Role of Rab27 protein family in drug resistance process of triple-negative breast cancer cells

  Background  Triple-negative breast cancer can only be treated by chemotherapy and immunotherapy due to its molecular expression patterns, but many patients have failed chemotherapy due to the emergence of multidrug resistance. Rab27 protein family is closely related to the secretion of exosomes, it is currently known that most of the mechanisms that enhance the efflux of chemotherapeutic drugs are mediated by exosomes. However, the specific roles of Rab27A and Rab27B, two members of this family, in the process of multi-drug resistance of triple-negative breast cancer cells are not yet clear.

  Objective  To explore the specific role and molecular mechanism of Rab27 protein family in the drug resistance process of triple-negative breast cancer cells by inhibiting its expression.

  Methods  After using siRNA to inhibit the expression of Rab27a and Rab27b in triple-negative breast cancer cells, western blotting was used to detect the secretion of exosomes. After Rab27a and Rab27b were inhibited, the cell viability under different concentrations of cisplatin, doxorubicin and paclitaxel were tested. Subsequently, the apoptosis and necrosis of tumor cells under the treatment of cisplatin, adriamycin and paclitaxel after inhibiting Rab27a and Rab27b were detected. Finally, the expression level of drug resistance-related genes in triple-negative breast cancer cells that inhibited Rab27a and Rab27b were detected.

  Results  After inhibiting the expression of Rab27a in triple-negative breast cancer cells, the secretion of exosomes was significantly down-regulated. However, inhibiting the expression of Rab27b had no significant effect on the secretion of exosomes. Inhibiting Rab27a and Rab27b reduced the tolerance of triple negative breast cancer cells to cisplatin, doxorubicin and paclitaxel, increased the apoptosis rate of tumor cells treated with these drugs, and decreased the expression level of drug-resistant related genes IL-6, EGR1, ABCC3 and ABCC6. The effect of inhibiting Rab27b on the drug resistance of tumor cells was significantly stronger than inhibiting Rab27a.

  Conclusion  The Rab27 family is closely related to the drug resistance of triple-negative breast cancer cells. Rab27a may be involved in the mechanism of drug resistance by promoting the release of exosomes. The molecular mechanism of Rab27b is different from Rab27a, and it may participate in the drug resistance mechanism of triple-negative breast cancer cells by regulating the expression of other resistance-related genes.