Effect of PI3K-mediated autophagy in human osteosarcoma MG63 cells on sensitivity to chemotherapy with cisplatin

Miao, Xudong; Cao, Le; Zhang, Qiang; Hu, Xiaoying; Zhang, Yi

doi:10.1016/j.apjtm.2015.07.024

Cited by 16 publications

(11 citation statements)

References 22 publications

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“…It could be hypothesized that miR-22 is able to inhibit autophagy induced by CDDP and decrease drug resistance via the PI3K/Akt/mTOR pathway both in vivo and in vitro. The results of the present study coincided with the results of a previous study, which revealed which PI3K could be downregulated to inhibit autophagy, leading to suppression of MG63 cell proliferation activity and increasing the sensitivity to CDDP (45). A recent study argued that miR-22-3p enhances the chemosensitivity of gastrointestinal stromal tumor cell lines to CDDP via the phosphatase and tensin homolog deleted on chromosome 10 (PTEN)/PI3K/Akt pathway (26).…”

Section: Discussionsupporting

confidence: 91%

MicroRNA‑22 mediates the cisplatin resistance of osteosarcoma cells by inhibiting autophagy via the PI3K/Akt/mTOR pathway

et al. 2020

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Osteosarcoma (OS) is the most common primary malignant tumor of the bone affecting children and adolescents. Chemotherapy is now considered as a standard component of OS treatment, not only for children, but also for adults. However, chemoresistance continues to pose a challenge to therapy. Inhibition of autophagy has been demonstrated to decrease chemoresistance in OS. Moreover, microRNA-22 (miR-22) inhibits autophagy, leading to an improvement in the sensitivity of cisplatin (CDDP) in OS. The aim of the present study was therefore to investigate whether miR-22 could mediate the CDDP resistance of OS cells by inhibiting autophagy via the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway. Cell proliferation assay, LC3 flow cytometry assay and monodansylcadaverine staining in MG63 cells and CDDP resistance cells (MG63/CDDP) were performed to explore to role of miR-22 and CDDP in OS chemoresistance. Inoculation of tumor cells in an in vivo model, reverse transcription-quantitative PCR (RT-qPCR) assay, western blot analysis, and immunohistochemistry analysis were performed to investigate the role of miR-22 and CDDP in the PI3K/Akt/mTOR pathway as it is affected by autophagy. The results revealed that miR-22 inhibited the proliferation of MG63 and MG63/CDDP cells, and enhanced the anti-proliferative ability of CDDP in vivo and in vitro. miR-22 mediated the CDDP resistance of OS cells by inhibiting autophagy and decreasing CDDP-induced autophagy via downregulation of the expression of PI3K, Akt, and mTOR at the mRNA level, and the expression of PI3K, phosphorylated (p)-Akt, and p-mTOR at the protein level. It was also convincingly demonstrated that miR-22 mediates the CDDP resistance of OS by inhibiting autophagy via the PI3K/Akt/mTOR pathway. Furthermore, in the MG63 cells that were affected by CDDP, the role of miR-22 was shown to be similar to that of the investigated inhibitor of PI3K (wortmannin) in terms of regulating the PI3K/Akt/mTOR pathway, and wortmannin could also promote the effect of miR-22. Interestingly, CDDP was demonstrated to induce autophagy by inhibiting the PI3K/Akt/mTOR pathway, whereas the pathway was upregulated in the state of chemoresistance. In conclusion, downregulation of the PI3K/Akt/mTOR pathway was shown to assist in the process of preventing chemoresistance.

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Section: Discussionsupporting

confidence: 91%

MicroRNA‑22 mediates the cisplatin resistance of osteosarcoma cells by inhibiting autophagy via the PI3K/Akt/mTOR pathway

et al. 2020

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“…Recently, autophagy has been reported as a mechanism by which osteosarcoma cells develop resistance to anti-tumor agents, including cisplatin and doxorubicin (27,28). Dysregulation of the p38 MAPK signaling pathway has an important role in tumor development and progression (29).…”

Section: Discussionmentioning

confidence: 99%

JNK pathway mediates curcumin-induced apoptosis and autophagy in osteosarcoma MG63 cells

Yao-wu

Chen

Han-gang

et al. 2017

Experimental and Therapeutic Medicine

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Human osteosarcoma is a common primary malignancy of the bone in children and adolescents. It has been reported that curcumin is able to induce apoptosis in osteosarcoma MG63 cells through the mitochondrial pathway. However, whether curcumin is able to induce autophagy and the interaction between apoptosis and autophagy in osteosarcoma cells has yet to be fully elucidated. In the current study, it was determined that curcumin was able to significantly induce apoptosis, and lead to autophagy in MG63 cells. Notably, inhibition of apoptosis enhanced curcumin-induced autophagy due to upregulation of the c-Jun N-terminal kinase (JNK) signaling pathway. This finding was confirmed by the use of JNK-specific inhibitor, SP600125. Furthermore, our data showed that curcumin-induced apoptosis was increased when autophagy was completely inhibited by 3-methyladenine in MG63 cells. These results suggest that autophagy may have an important role in resistance to apoptosis when MG63 cells are incubated with curcumin. Thus, these results provide important insights into the interaction between apoptosis and autophagy in osteosarcoma cells and clinical treatment strategies using curcumin.

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“…Flavonoid luteolin enhanced doxorubicin-induced autophagy in human osteosarcoma U2OS cells through upregulating beclin1, which revealed a synergistic cytotoxicity, leading to U2OS cell death [98]. The 3,4-dihydroxy-9,10-secoandrosta-1,3,5,7-tetraene-9,17-dione (DSTD), a novel androstenedione derivative, inhibited macrophage migration inhibitory factor (MIF) expression in MG-63 and U2OS cells.…”

Section: Programmed Cell Death In the Treatment Of Osteosarcomamentioning

confidence: 99%

Cell apoptosis, autophagy and necroptosis in osteosarcoma treatment

Yang

et al. 2016

Oncotarget

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Osteosarcoma is the most common primary bone tumor in children and adolescents. Although combined therapy including surgery and multi-agent chemotherapy have resulted in great improvements in the overall survival of patients, chemoresistance remains an obstacle for the treatment of osteosarcoma. Molecular targets or effective agents that are actively involved in cell death including apoptosis, autophagy and necroptosis have been studied. We summarized how these agents (novel compounds, miRNAs, or proteins) regulate apoptotic, autophagic and necroptotic pathways; and discussed the current knowledge on the role of these new agents in chemotherapy resistance in osteosarcoma.

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Effect of PI3K-mediated autophagy in human osteosarcoma MG63 cells on sensitivity to chemotherapy with cisplatin

Abstract: Up-regulating the autophagy significantly reduced the sensitivity of MG63 cell to chemotherapy with DDP. DDP induced autophagy of MG63 cell and blocked the cell cycle at G1 phase.

Cited by 16 publications

References 22 publications

MicroRNA‑22 mediates the cisplatin resistance of osteosarcoma cells by inhibiting autophagy via the PI3K/Akt/mTOR pathway

MicroRNA‑22 mediates the cisplatin resistance of osteosarcoma cells by inhibiting autophagy via the PI3K/Akt/mTOR pathway

JNK pathway mediates curcumin-induced apoptosis and autophagy in osteosarcoma MG63 cells

Cell apoptosis, autophagy and necroptosis in osteosarcoma treatment

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