Metformin inhibits the proliferation, metastasis, and cancer stem-like sphere formation in osteosarcoma MG63 cells in vitro

Xu, Chen; Hu, Chuanzhen; Zhang, Wei-Bin; Shen, Yuhui; Wang, Jun; Hu, Fangqiong; Yu, Pei

doi:10.1007/s13277-015-3751-1

Cited by 42 publications

(29 citation statements)

References 53 publications

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“…To the best of our knowledge, the present study shows for the first time the ability of metformin to inhibit the metastatic potential of endometrial epithelial cancer cells, while the metformin efficiency in the inhibition of migration and invasion has already been reported in a dose-dependent manner in other types of cancer cells, including ovarian (23) and prostate (31) cancer cells, and osteosarcoma (32). Recently, Han et al reported an increased ability of adhesion and invasion in two EC cell lines, suggesting that targeting glucose metabolism may be a promising therapeutic strategy for the treatment of EC (33).…”

Section: Discussionsupporting

confidence: 60%

Proliferation and metastatic potential of endometrial cancer cells in response to metformin treatment in a high versus normal glucose environment

et al. 2016

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Abstract. In order to improve our understanding of the potential preventive and therapeutic role of metformin, the present study aimed to investigate the capability of low-dose metformin in the efficient inhibition of cancer development and the reduction of the metastasis of endometrial adenocarcinoma type I and primary endometrial epithelial cells (eEPs), with the drug acting as a treatment in a hyperinsulinemic environment exposed to high and normal glucose conditions. The Ishikawa endometrial adenocarcinoma cell line and primary eEPs were exposed to an environment with high (17 mM) or normal glucose (5 mM) and treated with insulin, low-dose metformin (0.1 mM) or a combined treatment. Metastatic potential was assessed by migration and invasion assays, and relative cell proliferation was determined. Metformin at a low dose potently inhibited the insulin action, decreasing the ability of the endometrial cancer (EC) cell line to migrate and invade in a high and normal glucose environment, and decreasing the migration ability of the primary eEPs. In the EC cell line, the insulin treatment increased the proliferation, without any subsequent reduction of proliferation by the addition of 0.1 mM metformin; however, relative cell proliferation sensitivity to metformin was observed in the range between 1 and 5 mM regardless of the glucose concentration present. Overall, metformin at 0.1 mM is not efficient enough to decrease the proliferation in an EC cell line. However, at this concentration, metformin can inhibit the insulin action in endometrial epithelial cancer cells, demonstrating an anti-metastatic effect in high and normal glucose environments.

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Section: Discussionsupporting

confidence: 60%

Proliferation and metastatic potential of endometrial cancer cells in response to metformin treatment in a high versus normal glucose environment

et al. 2016

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“…However, other studies have shown that metformin exerts other effects beyond those on glucose metabolism, as by example to modulate inflammation in polycystic ovary syndrome [41] and to exert antiproliferative actions specially in cancer cells [42, 43]. These observations have expanded the range of actions of this drug that may explain several improvements not associated with its anti-hyperglycemic action [28].…”

Section: Discussionmentioning

confidence: 99%

Diabetic concentrations of metformin inhibit platelet-mediated ovarian cancer cell progression

et al. 2017

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Clinical studies have suggested a survival benefit in ovarian cancer patients with type 2 diabetes mellitus taking metformin, however the mechanism by which diabetic concentrations of metformin could deliver this effect is still poorly understood. Platelets not only represent an important reservoir of growth factors and angiogenic regulators, they are also known to participate in the tumor microenvironment implicated in tumor growth and dissemination. Herein, we investigated if diabetic concentrations of metformin could impinge upon the previously reported observation that platelet induces an increase in the tube forming capacity of endothelial cells (angiogenesis) and upon ovarian cancer cell aggressiveness. We demonstrate that metformin inhibits the increase in angiogenesis brought about by platelets in a mechanism that did not alter endothelial cell migration. In ovarian cancer cell lines and primary cultured cancer cells isolated from the ascitic fluid of ovarian cancer patients, we assessed the effect of combinations of platelets and metformin upon angiogenesis, migration, invasion and cancer sphere formation. The enhancement of each of these parameters by platelets was abrogated by the present of metformin in the vast majority of cancer cell cultures tested. Neither metformin nor platelets altered proliferation; however, metformin inhibited the increase in phosphorylation of focal adhesion kinase induced by platelets. We present the first evidence suggesting that concentrations of metformin present in diabetic patients may reduce the actions of platelets upon both endothelial cells and cancer cell survival and dissemination.

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“…Therefore, CSCs are believed to be of great importance in carcinogenesis, metastasis, drug-resistance and cancer recurrence. The existence of CSCs in osteosarcoma that are capable of forming suspended spherical, clonal colonies, preferentially express CSC key marker genes has been demonstrated [19]. EGCG could inhibit SOX2OT V7 which is closely related to pluripotency regulator SOX2 of CSCs, therefore, we speculated that EGCG would exert certain inhibitory effect on osteosarcoma stem cells (OSCs).…”

Section: Egcg Inhibited Dox-induced Autophagy By Targeting Sox2ot V7 mentioning

confidence: 95%

“…EGCG could inhibit SOX2OT V7 which is closely related to pluripotency regulator SOX2 of CSCs, therefore, we speculated that EGCG would exert certain inhibitory effect on osteosarcoma stem cells (OSCs). CD133 is considered to be the most common CSC marker, and has been used repeatedly for the successful isolation of osteosarcoma stem cells [19]. A growing number of studies have found that using immunomagnetic double positive screening could obtain CSCs with higher purity and stemness [20,21].…”

Section: Egcg Inhibited Dox-induced Autophagy By Targeting Sox2ot V7 mentioning

confidence: 99%

SOX2OT variant 7 contributes to the synergistic interaction between EGCG and Doxorubicin to kill osteosarcoma via autophagy and stemness inhibition

Wang

Chen

Zhu

2018

J Exp Clin Cancer Res

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Background: Doxorubicin is the preferred chemotherapeuticdrug for osteosarcoma treatment of which clinical efficacy is limited because of its chemo-resistance and cardiac toxicity. It is necessary to develop the combination regimen with complementary molecular mechanisms to reduce the side effects and enhance sensitivity of Doxorubicin. EGCG is a polyphenol in green tea with antitumor bioactivity,which has been found that its combination with certain chemotherapeutic drugs could improve the antitumor efficiency. Methods: In this study, MTT assay was used to detect the cell growth inhibition The CD133+/CD44+ cells were isolated from U2OS and SaoS2 cell lines using magnetic-activated cell sorting and identified by flow cytometry analysis. qRT-PCR was used for determining the relative mRNA levels of key genes. Immunofluorescence was performed to evaluate the autophagy flux alterations. Self-renewal ability was accessed by sphere-forming assay. Tumorigenicity in nude mice was preformed to evaluate tumorigenicity in vivo. Results: We found that EGCG targeting LncRNA SOX2OT variant 7 produced synergistic effects with Doxorubicin on osteosarcoma cell growth inhibition. On the one hand, EGCG could reduce the Doxorubicin-induced pro-survival autophagy through decreasing SOX2OT variant 7 to improve the growth inhibition of Doxorubicin. On the other hand, EGCG could partially inactivate Notch3/DLL3 signaling cascade targeting SOX2OT variant 7 to reduce the stemness then abated drug-resistance of osteosarcoma cells.

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Metformin inhibits the proliferation, metastasis, and cancer stem-like sphere formation in osteosarcoma MG63 cells in vitro

Cited by 42 publications

References 53 publications

Proliferation and metastatic potential of endometrial cancer cells in response to metformin treatment in a high versus normal glucose environment

Proliferation and metastatic potential of endometrial cancer cells in response to metformin treatment in a high versus normal glucose environment

Diabetic concentrations of metformin inhibit platelet-mediated ovarian cancer cell progression

SOX2OT variant 7 contributes to the synergistic interaction between EGCG and Doxorubicin to kill osteosarcoma via autophagy and stemness inhibition

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