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Polypeptide LTX‐315 reverses the cisplatin chemoresistance of ovarian cancer cells via regulating Beclin‐1/PI3K/mTOR signaling pathway
Author(s) -
Ma Jian,
Liu Lei,
Ling Yang,
Zheng Jianhua
Publication year - 2021
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.22853
Subject(s) - pi3k/akt/mtor pathway , apoptosis , protein kinase b , viability assay , chemistry , cisplatin , cancer research , autophagy , cell cycle , poly adp ribose polymerase , flow cytometry , cell growth , microbiology and biotechnology , biology , biochemistry , polymerase , chemotherapy , gene , genetics
Objective Polypeptide LTX‐315 induces immunogenic cell death, thus having the potential to improve the effect of anticancer treatment. However, the function of LTX‐315 in reversing chemoresistance in ovarian cancer (OC) still remains elusive. Our study aims to decipher the effect of LTX‐315 on reversing the chemoresistance of OC cells and explore its mechanism. Methods SKOV3, A2780, SKOV3/DDP, and A2780/DDP cells (cisplatin [DDP]‐resistant cells] were treated with different concentrations of LTX‐315 (10 and 20 µmol/L), respectively. Cell counting kit‐8 assay, Transwell assay, and flow cytometry were used to assess cell viability, migration, invasion, apoptosis rate, and cell cycle of the cells. Western blot was performed to examine the expression of cleaved caspase 3, caspase 3, cleaved Poly (ADP‐ribose) polymerase (PARP), PARP, Bax, Bcl‐2, Beclin‐1, p‐Akt, Akt, p‐mammalian target of rapamycin (mTOR), and mTOR. Furthermore, OC cells were treated with autophagy inhibitor 3‐methyladenine (3‐MA), and “rescue experiments” were performed. Results DDP‐resistant OC cell models were established, and LTX‐315 treatment resulted in lower IC 50 of DDP. In OC cells treated with LTX‐315, the viability, migration, invasion and the expression of Bcl‐2 of were repressed, but the apoptotic rate and the expression of cleaved caspase 3, cleaved PARP and Bax were increased, and the cell cycle was arrested. Moreover, LTX‐315 promoted Beclin‐1 expression level and inhibited p‐Akt and p‐mTOR expression levels, whereas 3‐MA could partially reverse the biological effects of LTX‐315 on OC cells. Conclusion LTX‐315 can inhibit the resistance of OC cells to DDP in vitro and plays a role by regulating Beclin‐1/phosphatidylinositol‐3‐kinase/mTOR signaling pathway.