PMID-sentid	Pub_year	Sent_text		comp_official_name	comp_offsetprotein_name	organism	prot_offset
34607979-7	2021	Metformin diminished the phosphorylation of mTOR, p70S6K and 4E-BP1 by accelerating adenosine monophosphateactivated kinase (AMPK) in HeLa cancer cells, but it did not affect other cell lines.	Metformin	0-9	ribosomal protein S6 kinase B1	Homo sapiens	50-56	
18495226-8	2008	Metformin growth inhibition was partly abolished by the AMPK inhibitor, compound C. Western blotting demonstrated that metformin at cytotoxic concentrations, induced AMPK phosphorylation and decreased p70S6K and S6K phosphorylation, suggesting the mechanism for its anti-proliferative action.	Metformin	0-9	ribosomal protein S6 kinase B1	Homo sapiens	201-207	
18495226-8	2008	Metformin growth inhibition was partly abolished by the AMPK inhibitor, compound C. Western blotting demonstrated that metformin at cytotoxic concentrations, induced AMPK phosphorylation and decreased p70S6K and S6K phosphorylation, suggesting the mechanism for its anti-proliferative action.	Metformin	119-128	ribosomal protein S6 kinase B1	Homo sapiens	201-207	
17698034-8	2007	Metformin treatment of the hepatocytes resulted in activation of the AMP-activated kinase, attenuation of the mTOR/S6K1 pathway, reduction of IRS-1 phosphorylation, and a leftward shift in the insulin dose-response curve for PKB activation.	Metformin	0-9	ribosomal protein S6 kinase B1	Homo sapiens	115-119	
35341775-0	2022	Metformin alleviates dexamethasone-induced apoptosis by regulating autophagy via AMPK/mTOR/p70S6K in osteoblasts.	Metformin	0-9	ribosomal protein S6 kinase B1	Homo sapiens	91-97	
35341775-12	2022	Treatment with the autophagy inhibitor 3-methyladenine (3-MA) attenuated the effect of metformin on apoptosis, autophagy, and the AMPK/mTOR/p70S6K signaling pathway.	Metformin	87-96	ribosomal protein S6 kinase B1	Homo sapiens	140-146	
35341775-15	2022	The AMPK/mTOR/p70S6K signaling pathway plays a role in metformin-mediated apoptosis suppression and autophagy promotion.	Metformin	55-64	ribosomal protein S6 kinase B1	Homo sapiens	14-20	
35341775-16	2022	In conclusion, metformin can alleviate Dex-induced osteoblast apoptosis by inducing autophagy via the AMPK/mTOR/p70S6K pathway.	Metformin	15-24	ribosomal protein S6 kinase B1	Homo sapiens	112-118	
34004440-8	2021	Inhibition of mTOR with rapamycin or knockdown of mTOR enhanced metformin"s suppression of hsBAFF-induced phosphorylation of S6K1, PTEN, Akt, and Erk1/2, as well as B-cell proliferation/viability.	Metformin	64-73	ribosomal protein S6 kinase B1	Homo sapiens	125-129	
32951587-5	2021	In this review, we summarize the chemosensitization effects of metformin and focus primarily on its molecular mechanisms in enhancing the sensitivity of multiple chemotherapeutic drugs, through targeting of mTOR, ERK/P70S6K, NF-kappaB/HIF-1alpha, and mitogenactivated protein kinase (MAPK) signaling pathways, as well as by down-regulating the expression of CSC genes and pyruvate kinase isoenzyme M2 (PKM2).	Metformin	63-72	ribosomal protein S6 kinase B1	Homo sapiens	217-223	
31028998-6	2019	More importantly, metformin induced G2/M cell cycle phase arrest in RA-FLS via the IGF-IR/PI3K/AKT/ m-TOR pathway and inhibited m-TOR phosphorylation through both the IGF-IR/PI3K/AKT signaling pathways thereby further upregulating and down-regulating p70s6k and 4E-BP1 phosphorylation, respectively; however, metformin was found not to induce apoptosis in RA-FLSs.	Metformin	18-27	ribosomal protein S6 kinase B1	Homo sapiens	251-268	
31926250-0	2020	Inhibition of mTORC1/P70S6K pathway by Metformin synergistically sensitizes Acute Myeloid Leukemia to Ara-C.	Metformin	39-48	ribosomal protein S6 kinase B1	Homo sapiens	21-27	
31926250-6	2020	KEY FINDINGS: We found that metformin could synergistically sensitize AML cells to Ara-C via inhibiting mTORC1/P70S6K pathway.	Metformin	28-37	ribosomal protein S6 kinase B1	Homo sapiens	111-117	
31926250-8	2020	SIGNIFICANCE: We firstly found the synergistic anti-tumor effect of Ara-C/metformin in AML through inhibiting mTORC1/P70S6K pathway.	Metformin	74-83	ribosomal protein S6 kinase B1	Homo sapiens	117-123	
31028998-7	2019	In summary, these results demonstrate that metformin can effectively inhibit RA-FLS proliferation through inducing cell cycle and upregulating and down-regulating p70s6k and 4E-BP1 phosphorylation.	Metformin	43-52	ribosomal protein S6 kinase B1	Homo sapiens	163-180	
30753544-3	2019	RESULTS: Metformin added to peripheral blood mononuclear cells from healthy volunteers enhanced in vitro cellular metabolism while inhibiting the mammalian target of rapamycin targets p70S6K and 4EBP1, with decreased cytokine production and cellular proliferation and increased phagocytosis activity.	Metformin	9-18	ribosomal protein S6 kinase B1	Homo sapiens	184-200	
30720062-5	2019	Western blot analysis demonstrated that treatment with metformin increased the phosphorylation of AMPK, and decreased the phosphorylation of AKT, mTOR and p70S6k.	Metformin	55-64	ribosomal protein S6 kinase B1	Homo sapiens	155-161	
30146703-9	2019	Contribution of mTOR signaling pathway in metformin-induced effect was shown by the inhibition of phosphorylation of S6K1 and 4E-BP1, the downstream targets of mTOR.	Metformin	42-51	ribosomal protein S6 kinase B1	Homo sapiens	117-121	
29728793-9	2018	Taken together, these findings suggest that metformin functions as a neuroprotective agent following SCI by promoting autophagy and inhibiting apoptosis by regulating the mTOR/P70S6K signaling pathway.	Metformin	44-53	ribosomal protein S6 kinase B1	Homo sapiens	176-182	
29472557-6	2018	Metformin reduced cyclin D1 expression and RB, STAT3, STAT5, ERK1/2 and p70S6K phosphorylation.	Metformin	0-9	ribosomal protein S6 kinase B1	Homo sapiens	72-78	
28406985-8	2017	To further explore the underlying mechanism, we found that metformin treatment could significantly damp the expression of 4EBP1 and S6K1 in KYSE 450 cells in vitro and in vivo, furthermore, the p-4EBP1 and p-S6K1 expression in KYSE 450 cells were also inhibited greatly in vitro and in vivo.	Metformin	59-68	ribosomal protein S6 kinase B1	Homo sapiens	132-136	
29085506-6	2017	Metformin significantly decreased E2-stimulated cell proliferation; an effect that was rescued in the presence of compound C. Metformin treatment markedly increased the phosphorylation of AMPK while decreasing p70S6K phosphorylation, indicating that metformin exerts its effects through stimulation of AMPK and subsequent inhibition of the mammalian target of rapamycin (mTOR) signaling pathway.	Metformin	0-9	ribosomal protein S6 kinase B1	Homo sapiens	210-216	
29085506-6	2017	Metformin significantly decreased E2-stimulated cell proliferation; an effect that was rescued in the presence of compound C. Metformin treatment markedly increased the phosphorylation of AMPK while decreasing p70S6K phosphorylation, indicating that metformin exerts its effects through stimulation of AMPK and subsequent inhibition of the mammalian target of rapamycin (mTOR) signaling pathway.	Metformin	126-135	ribosomal protein S6 kinase B1	Homo sapiens	210-216	
27857021-9	2017	Further study revealed that metformin could suppress the expression of insulin-like growth factor 1 receptor and its downstream proteins, phosphoinositide 3-kinase (PI3K), protein kinase B (AKT/PKB), phosphorylation of AKT (pAKT), mammalian target of rapamycin (mTOR), p70S6K, and PKM2.	Metformin	28-37	ribosomal protein S6 kinase B1	Homo sapiens	269-275	
28406985-8	2017	To further explore the underlying mechanism, we found that metformin treatment could significantly damp the expression of 4EBP1 and S6K1 in KYSE 450 cells in vitro and in vivo, furthermore, the p-4EBP1 and p-S6K1 expression in KYSE 450 cells were also inhibited greatly in vitro and in vivo.	Metformin	59-68	ribosomal protein S6 kinase B1	Homo sapiens	208-212	
27916907-10	2016	CONCLUSION: Metformin abolishes TGF-beta1-induced EMT in cervical carcinoma cells by inhibiting mTOR/p70s6k signaling to down-regulate PKM2 expression.	Metformin	12-21	ribosomal protein S6 kinase B1	Homo sapiens	101-107	
27856287-4	2017	Spinal local application of AMPK agonist metformin (25mug) prevented the long term potentiation (LTP) induction and the activation of mTOR/p70S6K signal pathway, and significantly attenuated the acute thermal hyperalgesia and mechanical allodynia following single oxaliplatin treatment.	Metformin	41-50	ribosomal protein S6 kinase B1	Homo sapiens	139-145	
27856287-8	2017	Local application of metformin significantly decreased the mTOR and p70S6K activation induced by tetanus stimulation or oxaliplatin (i.p.).	Metformin	21-30	ribosomal protein S6 kinase B1	Homo sapiens	68-74	
27128966-8	2017	The activation of GSK3beta correlated with the inhibitory phosphorylation by Akt as well as p70S6K through AMPK activation in response to metformin.	Metformin	138-147	ribosomal protein S6 kinase B1	Homo sapiens	92-98	
27404348-6	2016	Metformin activated the AMPK/mTOR signaling pathway as shown by increased p-AMPK and decreased p-p70S6K.	Metformin	0-9	ribosomal protein S6 kinase B1	Homo sapiens	97-103	
27916907-0	2016	Metformin Inhibits TGF-beta1-Induced Epithelial-to-Mesenchymal Transition via PKM2 Relative-mTOR/p70s6k Signaling Pathway in Cervical Carcinoma Cells.	Metformin	0-9	ribosomal protein S6 kinase B1	Homo sapiens	97-103	
27916907-9	2016	Metformin decreased the p-p70s6k expression and the blockade of mTOR/p70s6k signaling decreased PKM2 expression.	Metformin	0-9	ribosomal protein S6 kinase B1	Homo sapiens	26-32	
26669511-10	2016	Collectively, these findings establish a clear relationship between cation-selective transporter expression, the AMPK-mTOR-pS6K signaling cascade, and the antiproliferative activity of metformin in breast cancer.	Metformin	185-194	ribosomal protein S6 kinase B1	Homo sapiens	123-127	
27246734-6	2016	Western blot revealed that the expression of Beclin-1 and LC3B-II was enhanced, and the phosphorylation levels of the mammalian target of rapamycin (mTOR) protein and p70S6K were reduced by metformin after SCI.	Metformin	190-199	ribosomal protein S6 kinase B1	Homo sapiens	167-173	
27246734-9	2016	Hence, metformin attenuated SCI by inhibiting apoptosis and inflammation and enhancing the autophagy via the mTOR/p70S6K signalling pathway.	Metformin	7-16	ribosomal protein S6 kinase B1	Homo sapiens	114-120	
26305116-10	2016	Metformin at 50 mM significantly reduced the phosphorylation of mTOR and p70S6K, by 49.0 and 62.1%, respectively.	Metformin	0-9	ribosomal protein S6 kinase B1	Homo sapiens	73-79	
27135362-8	2016	These hypotheses were tested in vivo; as a proof-of-principle, we demonstrated that metformin inhibits the p70S6K-rpS6 axis in a PP2A-phosphatase dependent manner.	Metformin	84-93	ribosomal protein S6 kinase B1	Homo sapiens	107-113	
26304716-6	2015	Finally, metformin-mediated AMPK/mTOR/p70S6K was identified as a possible upstream pathway controlling translational regulation of Wee1 and Rad51.	Metformin	9-18	ribosomal protein S6 kinase B1	Homo sapiens	38-44	
26344902-9	2015	To understand this more, we show activation of AMPK by metformin also prevented palmitate-induced changes in the phosphorylations of raptor and p70S6K, confirming that the mTORC1/p70S6K signaling pathway is responsive to AMPK activity.	Metformin	55-64	ribosomal protein S6 kinase B1	Homo sapiens	144-150	
26344902-9	2015	To understand this more, we show activation of AMPK by metformin also prevented palmitate-induced changes in the phosphorylations of raptor and p70S6K, confirming that the mTORC1/p70S6K signaling pathway is responsive to AMPK activity.	Metformin	55-64	ribosomal protein S6 kinase B1	Homo sapiens	179-185	
25817233-11	2015	Co-treatment with metformin or AICAR decreased the TNF-alpha-induced intracellular TG, accompanied by significantly enhanced AMPK and ACC phosphorylation, suppressed mTOR and p70S6K phosphorylation, and reduced SREBP-1 and FAS expressions.	Metformin	18-27	ribosomal protein S6 kinase B1	Homo sapiens	175-181	
26391180-0	2015	Metformin Increases Sensitivity of Pancreatic Cancer Cells to Gemcitabine by Reducing CD133+ Cell Populations and Suppressing ERK/P70S6K Signaling.	Metformin	0-9	ribosomal protein S6 kinase B1	Homo sapiens	130-136	
25921843-9	2015	Compared to baseline, metformin significantly improved metabolic parameters and insulin sensitivity, increased SIRT1 gene/protein expression and SIRT1 promoter chromatin accessibility, elevated mTOR gene expression with concomitant reduction in p70S6K phosphorylation in subjects" PBMCs, and modified the plasma N-glycan profile.	Metformin	22-31	ribosomal protein S6 kinase B1	Homo sapiens	245-251	
25921843-10	2015	Compared to placebo, metformin increased SIRT1 protein expression and reduced p70S6K phosphorylation (a proxy of mTOR activity).	Metformin	21-30	ribosomal protein S6 kinase B1	Homo sapiens	78-84	
24714080-6	2014	However, metformin inhibited the mTOR/S6K1 pathway in 253J and RT4 cells, which usually regulates protein translation; moreover, knockdown of S6K1 effectively reduced the levels of c-FLIPL, indicating that metformin downregulates c-FLIP through inhibition of the mTOR/S6K1 pathway.	Metformin	206-215	ribosomal protein S6 kinase B1	Homo sapiens	142-146	
24714080-8	2014	Taken together, our results indicate that metformin sensitizes human bladder cancer cells to TRAIL-induced apoptosis through downregulation of c-FLIP, which is mediated by the mTOR/S6K1 pathway, but independent of AMPK; furthermore, these findings provide a rationale for the combined application of metformin with TRAIL in the treatment of bladder cancer.	Metformin	42-51	ribosomal protein S6 kinase B1	Homo sapiens	181-185	
24858012-8	2014	In MCF-7 cells metformin decreased the activation of IRbeta, Akt and ERK1/2, increased p-AMPK, FOXO3a, p27, Bax and cleaved caspase-3, and decreased phosphorylation of p70S6K and Bcl-2 protein expression.	Metformin	15-24	ribosomal protein S6 kinase B1	Homo sapiens	168-174	
24714080-0	2014	Metformin sensitizes human bladder cancer cells to TRAIL-induced apoptosis through mTOR/S6K1-mediated downregulation of c-FLIP.	Metformin	0-9	ribosomal protein S6 kinase B1	Homo sapiens	88-92	
24714080-6	2014	However, metformin inhibited the mTOR/S6K1 pathway in 253J and RT4 cells, which usually regulates protein translation; moreover, knockdown of S6K1 effectively reduced the levels of c-FLIPL, indicating that metformin downregulates c-FLIP through inhibition of the mTOR/S6K1 pathway.	Metformin	9-18	ribosomal protein S6 kinase B1	Homo sapiens	38-42	
24714080-6	2014	However, metformin inhibited the mTOR/S6K1 pathway in 253J and RT4 cells, which usually regulates protein translation; moreover, knockdown of S6K1 effectively reduced the levels of c-FLIPL, indicating that metformin downregulates c-FLIP through inhibition of the mTOR/S6K1 pathway.	Metformin	9-18	ribosomal protein S6 kinase B1	Homo sapiens	142-146	
24714080-6	2014	However, metformin inhibited the mTOR/S6K1 pathway in 253J and RT4 cells, which usually regulates protein translation; moreover, knockdown of S6K1 effectively reduced the levels of c-FLIPL, indicating that metformin downregulates c-FLIP through inhibition of the mTOR/S6K1 pathway.	Metformin	9-18	ribosomal protein S6 kinase B1	Homo sapiens	142-146	
24714080-6	2014	However, metformin inhibited the mTOR/S6K1 pathway in 253J and RT4 cells, which usually regulates protein translation; moreover, knockdown of S6K1 effectively reduced the levels of c-FLIPL, indicating that metformin downregulates c-FLIP through inhibition of the mTOR/S6K1 pathway.	Metformin	206-215	ribosomal protein S6 kinase B1	Homo sapiens	142-146	
24505341-10	2014	Furthermore, hyperthermia potentiated the effect of metformin to activate AMPK and inactivate mTOR and S6K.	Metformin	52-61	ribosomal protein S6 kinase B1	Homo sapiens	103-106	
23709654-9	2013	In vitro data revealed that metformin inhibited cancer cell growth, activated cAMP-inducible protein kinase (5"-AMP-activated protein kinase [AMPK]), and down-regulated p70S6K/pS6.	Metformin	28-37	ribosomal protein S6 kinase B1	Homo sapiens	169-175	
24750786-3	2014	Metformin exerts anticancer effects by primarily blocking the pivotal LKB1/AMPK/mTOR/S6K1 pathway-dependent cell growth, induces selective lethal effects on GSC by impairing the GSC-initiating spherogenesis and inhibits the proliferation of CD133+ cells, while having a low or null effect on differentiated glioblastoma cells and normal human stem cells.	Metformin	0-9	ribosomal protein S6 kinase B1	Homo sapiens	85-89	
23709654-10	2013	Metformin potentiated H2O2-inducible activation of AMPK but attenuated pERK and p70S6K.	Metformin	0-9	ribosomal protein S6 kinase B1	Homo sapiens	80-86	
23709654-14	2013	In vitro data suggest that p70S6K/pS6 is likely a molecular target of metformin in DTC cells.	Metformin	70-79	ribosomal protein S6 kinase B1	Homo sapiens	27-33	
24335168-4	2013	Treatment with metformin was also associated with activation of AMP kinase and inhibition of mTOR/p70S6K/pS6 signaling in both cells.	Metformin	15-24	ribosomal protein S6 kinase B1	Homo sapiens	98-104	
23449430-0	2013	Metformin impairs vascular endothelial recovery after stent placement in the setting of locally eluted mammalian target of rapamycin inhibitors via S6 kinase-dependent inhibition of cell proliferation.	Metformin	0-9	ribosomal protein S6 kinase B1	Homo sapiens	148-157	
22389381-7	2012	Treatment with metformin was associated with inhibition of mTOR/p70S6K/pS6 signaling and downregulation of pERK in both TT and MZ-CRC-1 cells.	Metformin	15-24	ribosomal protein S6 kinase B1	Homo sapiens	64-70	
22500211-5	2012	Both metformin and ionizing radiation activated AMPK leading to inactivation of mTOR and suppression of its downstream effectors such as S6K1 and 4EBP1, a crucial signaling pathway for proliferation and survival of cancer cells, in vitro as well as in the in vivo tumors.	Metformin	5-14	ribosomal protein S6 kinase B1	Homo sapiens	137-151	
21168492-7	2011	In parallel, IGF-II increases phosphorylation of AKT and p70S6K, while metformin increases AMPK phosphorylation and decreases p70S6K phosphorylation.	Metformin	71-80	ribosomal protein S6 kinase B1	Homo sapiens	126-132	
21168492-8	2011	The effects of metformin on PR A/B and p70S6K are partially reversed by an AMPK inhibitor.	Metformin	15-24	ribosomal protein S6 kinase B1	Homo sapiens	39-45	
20363874-3	2010	The AMPK activator metformin stimulated AMPK Thr172 phosphorylation and inhibited IGF-I-stimulated phosphorylation of Akt/tuberous sclerosis 2 (TSC2)/mammalian target of rapamycin (mTOR)/p70S6 kinase (p70S6K).	Metformin	19-28	ribosomal protein S6 kinase B1	Homo sapiens	201-207	
21717584-6	2011	Mammalian target of rapamycin complex 1 (mTORC1), which is negatively regulated by AMPK and plays a central role in cell growth and proliferation, was inhibited by metformin, as manifested by dephosphorylation of its downstream targets 40S ribosomal S6 kinase 1 (S6K1) (T389), the eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1) (T37/46) and S6 (S235/236) in C666-1 cells.	Metformin	164-173	ribosomal protein S6 kinase B1	Homo sapiens	263-267