miR-203 is a tumor suppressor which participates in the pathogenesis of many tumors including lung adenocarcinoma. However, the role of miR-203 in suppressing chemotherapy resistance to cisplatin (cis-diamminedichloroplatinum; DDP) as well as its molecular mechanism is still to be determined in lung adenocarcinoma. In this study, we found that miR-203 decreased lung cancer cell migration and invasion, and that increased miR-203 expression sensitized lung adenocarcinoma cells to DDP in vitro. Furthermore, ZEB2 was found to be a direct target of miR-203, which induces epithelial-mesenchymal transition (EMT) signal. Knock-down of ZEB2 significantly increased DDP chemosensitivity in lung adenocarcinoma. More interestingly, we also demonstrated that ZEB2 could directly bind to E-box of the miR-203 promoter and suppress its expression in lung adenocarcinoma. Our data reveal that miR-203 serves as a negative feedback by directly suppressing the upstream ZEB2 gene, which inhibits EMT signaling and reduces chemoresistance of DDP. Together, these results highlight a feedback loop between miR-203 and ZEB2, which participates in the pathogenesis of lung adenocarcinoma.

Background. Nasopharyngeal carcinoma (NPC) is an invasive squamous cell carcinoma located in the nasopharynx. NPC has a high recurrence risk after initial treatment due to its high metastatic and immune escape potential. One study has found that metformin can improve cancer outcomes and reduce cancer incidence. Objective. With antitumor activity, metformin can have low toxicity when used in combination with some common chemotherapy drugs. This study was designed to explore the effects of cisplatin combined with metformin on the proliferation and apoptosis of nasopharyngeal carcinoma (NPC) cells. Methods. An appropriate cisplatin concentration was selected for NPC cells, and the cells were treated with metformin at a gradient concentration, and then, some of them were treated with cisplatin. Subsequently, the biological effects (activity, migration, invasion, and apoptosis) of metformin alone and metformin combined with cisplatin on NPC cells were evaluated. Results. Metformin alone inhibited cell activity, migration, and invasion and promoted cell apoptosis in a concentration-dependent and time-dependent manner, while compared with cisplatin alone, cisplatin combined with metformin had stronger inhibition on cell activity, migration, and invasion and stronger induction to cell apoptosis, and a higher concentration of them demonstrated stronger effects. Conclusion. Cisplatin combined with metformin can strongly inhibit the activity of NPC cells and promote their apoptosis.

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) License.