Inhibition effect of Hsp90 on TLR2, TLR4, and MAPK signaling pathway in melanoma in-vitro

Abstract

IntroductionThe Hsp90 is a member of heat shock proteins (HSPs) involved in protein folding and protecting cells from stress. Hsp90 is implicated in melanoma carcinogenesis in which its suppression could have beneficial applicability. This study aimed to investigate the effect of Hsp90 inhibition on TLR2 and TLR4 expression along with the MAPK signaling pathway in melanoma cancer cell line (A-375). Materials & methodsMelanoma cell line was exposed to Hsp90 inhibitor. After 48 h, the expression of Hsp90 was determined by Real-Time PCR and Western blotting. Then, TLR2 and TLR4 expression levels along with phosphorylated p38, ERK, JNK (MAPK signaling pathway) were assessed by qRT-PCR and Western blotting. MTT assay was used to determine the effect of Hsp90 inhibition on cell proliferation. ResultsThe Hsp90 inhibitor decreased the expression of Hsp90 after 48 h. This decrement led to decreased expression of TLR2 and TLR4 through the MAPK signaling pathway in melanoma cells. MTT assay revealed that anti- Hsp90 treatment caused a reduction of cell viability in a time-dependent manner. ConclusionThe results of this study determine the potential therapeutic ability of Hsp90 inhibitor in melanoma skin cancer cells by regulating TLR2 and TLR4 through MAPK signaling pathway in-vitro.