Low temperature upregulating HSP70 expression to mitigate the paclitaxel-induced damages in NHEK cell

Abstract

Scalp cooling is the most approved treatment for preventing chemotherapy-induced alopecia (CIA). However, the protective mechanism of scalp cooling has rarely been reported. The goal of the present study was to study the relationship between paclitaxel concentration and temperature and the inhibitory effect of low temperature on paclitaxel-induced alopecia. The results showed that the dose of paclitaxel should not exceed 60–70 mg/mL during scalp cooling treatment, and the optimal cooling temperature under different paclitaxel concentrations was determined. Normal human epidermal keratinocytes (NHEK) cells were analyzed by global transcriptome analysis, functional annotation and pathway analysis of differentially expressed genes (DEGs) and ELISA kit to analyze the mechanism of low temperature therapy. The expression of HSPA8, HSPA1A and HSPA1B, which belongs to HSP70, was up-regulated by low temperature. These genes are important target genes of low temperature treatment, which were confirmed by ELISA. The up-regulation of PLK2 and the down-regulation of TXNIP expression are the upstream of mitochondrial dysfunction and ROS, inhibiting the accumulation of ROS and up-regulating the mitochondrial membrane potential. Our research partially elucidates the therapeutic mechanism of scalp cooling, which provides a new idea on the drug research and development in CIA.