Mechanism Of Non-thermal Atmospheric Plasma Effects On Breast Cancer Cell Proliferation And Drug-resistance

Plasma is the fourth fundamental state of matter in the universe and biological plasma effects are transmitted through gas and liquid environment.Non-thermal atmospheric plasma (NTP) has shown its selective anticancer effects in many types of tumors in vitro and one of the main mechanisms is that NTP can induce different increase of intracellular ROS in cancer and homologous normal cells. Here, we report that NTP treatment reduces the proliferation of triple negative breast cancer (TNBC) and normal cell lines. Simultaneously, STAT3 pathway is inhibited by NTP effects. However, normal cells MCF1OA are more sensitive to ROS toxicity induced by NTP than cancer cells MDA-MB-231. When ROS inhibitor N-acetyl cysteine (NAC) is employed in NTP treatments, the proliferation of normal breast cells MCF10A recovers. Meanwhile, NTP effects remain significant inhibition of MDA-MB-231 cells. Our results further reveal that NTP can induce apoptosis in MDA-MB-231 cells through inhibiting interleukin-6 receptor (IL-6R) pathway.Moreover, the mechanism of NTP anti-cancer selectivity relates to constantly HER2/Akt activation induced by NTP especially in MCF10A cells but not in MDA-MB-231 cells. Therefore, using ROS scavenger with NTP treatments may be a feasible strategy to TNBC cells.The combination of NTP and antitumor drugs treatments have surprising outcomes in a synergistic anti-cancer treatment. Breast cancer patients treated with tamoxifen or doxorubicin may gain chemoresistance to these drugs. We observed that NTP activated medium (PAM) treatments could induce the reversal of tamoxifen and doxorubicin resistance. Furemore, we observed a great decreased cell viability when treated the tamoxifen-resistant (TamR) or doxorubicin-resistant (ADR) cells with the combination of PAM and tamoxifen or doxorubicin. It was reported that?-CATENIN plays a key role in tamoxifen resistance of breast cancer cells. We shown that PAM can significantly inhibit the proportion of cancer stem cells in TamR cells through inhibits the P-CATENIN pathway. PAM can also inhibit the MDR1 expression to reverse the resistant effect in ADR cells. In conclusion, the above results indicate that NTP may be a potential anti-cancer therapy for drug resistant patients.