ABSTRACT
Cisplatin-based chemotherapy is commonly used for cervical cancer treatment. However, the development of chemoresistance is considered the main obstacle to the effectiveness of this therapeutic agent. MicroRNAs are illustrated to play a major role in the regulation of cancer cell chemosensitivity. Therefore, this study was aimed to investigate the potential therapeutic role of miRNA-143 in combination with cisplatin on cervical cancer cells. Then, CaSki cell line with low expression levels of miRNA-143 was selected for functional experiments. The cells were treated with miRNA-143 and cisplatin individually or in combination. The cell viability and apoptosis induction were evaluated by MTT, Annexin V-FITC/PI, and DAPI staining tests. Cell migration was further evaluated by wound healing assay. The effect of miRNA-143 and cisplatin combination on gene expression was quantified by real-time PCR. Furthermore, the combination therapy effect on cell cycle progression and autophagy induction was also evaluated by flow cytometry. Our results showed that miRNA-143 overexpression could increase cisplatin-induced apoptosis and increase the sensitivity of CaSki cells to low doses of this chemotherapeutic agent via modulating the expression of apoptosis-related genes including Bcl-2, Bax, and caspase-9. Besides, miRNA-143 and cisplatin were demonstrated to cooperatively increase the cell cycle arrest at the sub-G1 and G2-M phases, induce autophagy activation, and via downregulation of vimentin inhibit CaSki cell migration. Moreover, c-Myc as an important regulator of cell growth was downregulated in treatment groups compared to the control. In conclusion, regarding that miRNA-143 could sensitize cervical cancer cells to cisplatin, it may be considered a promising therapeutic strategy for the treatment of this malignancy.
