The tissue transglutaminase: a potential target regulating MDR in breast cancer.
Eur Rev Med Pharmacol Sci. 2020 Jun;24(11):6175-6184
Authors: Cheng K, Wang XH, Hua YT, Zhang YZ, Han Y, Yang ZL
OBJECTIVE: Multi-drug resistance (MDR) is the main obstacle influencing the anti-tumor effect in breast cancer. To date, no proper potential targets are found to overcome MDR. Here, tTG was explored to show whether it is a potential target to regulate MDR in breast cancer.
MATERIALS AND METHODS: tTG was silenced by small interfere siRNA. After that, the mRNA level of CD44, CD24, LRP, MRP and MDR1 were detected by RT-PCR. The Western blot analysis was used to detect the expression of LRP, P-gp and MRP. In addition, the impact of tTG on cell apoptosis, as well as cell proliferation were observed. Finally, to evaluate the role of tTG in BALB/c nude mice, the growth of tumor was performed, and the immunohistochemistry analysis was used to observe the expression of LRP, P-gp and MRP in vivo.
RESULTS: In MCF-7/ADR, Compared to MCF-7, tTG expression was highly increased. After silencing tTG, the mRNA level and the protein level of P-gp, MRP, LRP were both differently decreased. The mRNA level of CD44 and CD24 was also down-regulated after silencing tTG. In addition, the cell proliferation was significantly inhibited in the ADR + tTG siRNA+Adriamycin group (p<0.05), and the tumor growth was prevented in a time-dependent situation. Cell apoptosis was significantly strengthened in the ADR+tTG siRNA+Adriamycin group (p<0.05). In vivo, the growth of tumors was reduced after silencing tTG, and the LRP, P-gp and MRP expression were significantly down-regulated in ADR + tTG SiRNA +adriamycin group (p<0.05).
CONCLUSIONS: It is concluded that the tTG may be a potential target regulating the MDR by regulating LRP, P-gp and MRP expression as well as the expression of CD44CD24 to improve the MDR in breast cancer.
PMID: 32572883 [PubMed - in process]