A nanomicelle with miR-34a and doxorubicin reverses the drug resistance of cisplatin in esophageal carcinoma cells by inhibiting SIRT1 signal pathway

Background: Esophageal carcinoma (EC) is one of the most deadly malignant tumors in the world. Surgery, combined with chemotherapy or radiotherapy, is the traditional strategy for the treatment of EC. Cisplatin (CDDP) is a common chemotherapy drug widely used to treat EC due to its powerful anti-tumor effect. However, CDDP is subject to intrinsic or acquired resistance in EC cells, which badly hinders the efficacy of chemotherapy. The resistance phenomenon is mostly caused by the p53 mutant in the EC and the low efficiency of the drug delivery system. Methods: In this study, a specially designed nanomicelle was used to promote the anti-tumor effect of chemotherapy drugs against the CDDP-resistant EC cells. The nanomicelle consisted of miR-34a, doxorubicin (DOX), polyethylene glycol (PEG), and other excipients in an appropriate ratio. Results: The results showed that the nanomicelle could exert significant cell proliferation inhibition and apoptosis-inducing effects in the CDDP-resistant EC cells. The endogenous expression of miR-34a in the CDDP-resistant EC cells was promoted by the incubation with the nanomicelle. After incubation with the nanomicelle, the expression of protein SIRT1 was inhibited, and the expression of caspase3 was promoted significantly in the CDDP-resistant EC cells. Conclusions: Our results indicate that the specially designed nanomicelle can exert promising anti-tumor effects by introducing miR-34a to inhibit SIRT1 signaling pathway and enhance the efficiency of the drug delivery system.