Low temperature mitigating the paclitaxel-induced damages in mouse cell and hair follicle model

Abstract

Scalp cooling is currently the most approved treatment to prevent alopecia due to chemotherapy for cancer. Few reports can be available, and the mechanisms involved in scalp cooling were unclear. The present work tries to reveal a preliminary inhibitory mechanism of scalp cooling on paclitaxel-induced alopecia. The results found that low temperature enhanced local vasoconstriction to 0.32 (dimensionless diameter, @ 22°C) and the vascular diameter presented an oscillating attenuation, which led to the concentration reduction of chemotherapeutic drugs transported by blood flow. Cooling significantly rescued M-HFK cells treated by paclitaxel, and the lower temperature for the better protection due to weakening the cytotoxicity in some extent. Cell cycle results showed that the G0/G1 phase was arrested at low temperature (i.e. 22°C), which was beneficial to mitigate the effect of paclitaxel on the G2/M phase cycle and finally made the cell cycle return to normal. Also, cold stimulation significantly increased the concentration of HSP70 more than 3 times (@22°C for 2h) compared with that of the control group, which means low temperature can protect cells from stresses. Furtherly, Cooling reduced the number of PH3+ and Caspase-3+ cells in the hair follicle, and effectively inhibited the cell apoptosis in the vitro hair follicle and alopecia in the mice experiments. The current work provides a basis for deeply understanding the chemotherapy-induced alopecia prevention with scalp cooling.