Curcumin Enhances Sensitivity to Cisplatin in Cervical Cancer Cells through AKT/mTOR Pathway Inhibition

Introduction: The objective is to examine how curcumin influences cell proliferation and autophagy in cisplatin-resistant cervical cancer cell lines, HeLa and SiHa, by modulating the phosphorylation of the AKT/mTOR signaling pathway. Methods: Cisplatin-resistant cervical cancer cell lines, HeLa/DDP and SiHa/DDP, were established via the concentration escalation method, which was subsequently validated for its resistance phenotype through functional assays, including inhibitory coefficient (IC)50 and resistance index (RI) determination. Cisplatin-resistant cervical cancer cells were stimulated with or without curcumin at 8.5 μM. After 48 hours of treatment, cell proliferation was evaluated by the CCK-8 assay, and immunoblotting was used to detect autophagy-related proteins, LC3II/I, and Beclin-1; in addition, the phosphorylations of AKT and mTOR proteins were evaluated. Results: The IC50 values for cisplatin-resistant cells were 39.34 ng/mL and 37.12 ng/mL of HeLa and SiHa, whereas in the control group of cells, the IC50 values were 7.29 ng/mL and 6.73 ng/mL of HeLa and SiHa. The resistance indices (RIs) of HeLa and SiHa were 5.4 and 5.52, respectively. In relation to the control group, the curcumin significantly reduced cell proliferation rates, reduced phosphorylation of Akt and mTOR, and increased expression of LC3II/I as well as Beclin-1 (P<0.05). In contrast, activation of mTOR by MHY1485 significantly restored the proliferation of both cell lines and reduced the expression of autophagy-related proteins (all P < 0.01). Discussion: This research demonstrated that curcumin suppressed the growth of drug-resistant cervical cancer cells and enhanced autophagy by reducing the phosphorylation of the AKT/mTOR signaling pathway, offering a novel avenue for overcoming drug resistance. Conclusion: Curcumin promotes autophagy and inhibits proliferation in cisplatin-resistant cervical cancer HeLa and SiHa cells by regulating phosphorylation of the AKT/mTOR signaling pathway.