Reversing Sunitinib Resistance Facilitated by ITGA1 Through the PI3K/Akt/Bcl-2 Pathway Using Nano Co-Delivery System in Renal Cell Carcinoma

Abstract

For genitourinary cancers, renal cell carcinoma (RCC) is the third leading cause of death, while target drug resistance has always been a difficult problem. Integrin alpha 1 (ITGA1) is a member of the integrin family, which is significant for the pathogenesis, development, and drug resistance of various malignant tumors. However, it remains unclear for the ITGA1 functions in renal cell carcinoma sunitinib resistance. In this study, we found that the ITGA1 gene facilitates renal cell carcinoma sunitinib resistance through the PI3K/Akt/Bcl-2 signaling pathway. Based on this, we developed a co-delivery system designated as Su/Si-PEAL NPs for the synergistic delivery of ITGA1 small interfering RNA (siRNA) and sunitinib using monomethoxy polyethylene glycol-polylactic acid/glycolic acid-poly-L-lysine triblock copolymer (mPEG-PLGA-PLL, PEAL) as the backbone material. Furthermore, the results of a series of functional experiments confirmed that this codelivery system was capable of downregulating the expression of ITGA1 and enhancing the sensitivity of 786-O-R cells to sunitinib. This co-delivery system could be an efficient approach for reversing sunitinib resistance in renal cell carcinoma.