Abstract
Enzalutamide is a drug used to treat prostate cancer (PC) and docetaxel is a drug for chemotherapeutic treatment of diverse cancer types, including PC. The effectiveness of these drugs in treating castration-resistant prostate cancer (CRPC) is poor and therefore CRPC is still largely incurable. However, the bio-inhibitor of fatty acid-binding protein 5 (FABP5), dmrFABP5, which is a mutant form of FABP5 incapable of binding to fatty acids, has been shown recently to be able to suppress the tumorigenicity and metastasis of cultured CRPC cells. The present study investigated the possible synergistic effect of dmrFABP5 combined with either enzalutamide or docetaxel on suppressing the tumorigenic properties of PC cells, including cell viability, migration, invasion and colony proliferation in soft agar. A highly significant synergistic inhibitory effect on these properties was observed when dmrFABP5 was used in combination with enzalutamide on androgen-responsive PC 22RV1 cells. Moreover, a highly significant synergistic inhibitory effect was also observed when dmrFABP5 was combined with docetaxel, and added to 22RV1 cells and to the highly malignant, androgen-receptor (AR)-negative Du145 cells. DmrFABP5 alone failed to produce any suppressive effect when added to the FABP5-negative cell line LNCaP, although enzalutamide could significantly suppress LNCaP cells when used as a single agent. These synergistic inhibitory effects of dmrFABP5 were produced by interrupting the FABP5-related signal transduction pathway in PC cells. Thus, dmrFABP5 appears to be not only a potential single therapeutic agent, but it may also be used in combination with existing drugs to suppress both AR-positive and AR-negative PC.