CMBs carrying PTX and CRISPR/Cas9 targeting C‑erbB‑2 plasmids interfere with endometrial cancer cells.

Abstract

Development of combination therapy to decrease side effects of chemotherapeutic drugs and increase their utilization rate in combination with gene editing is a key research topic in tumor treatment. The present study aimed to investigate the effect of cationic microbubbles (CMBs) carrying paclitaxel (PTX) and C-erbB-2 knockout plasmid on the endometrial cancer cell line HEC-1A and to determine how C-erbB-2 regulates the function of endometrial cancer cells. Cells were treated with CMB, PTX, PTX-CMBs, cationic plasmid-carrying or cationic PTX-carrying plasmid groups. After verifying the most effective combination of PTX-CMBs and plasmids, HEC-1A cells were transfected. Reverse transcription-quantitative (RT-q)PCR and western blotting were used to measure C-erbB-2 and protein expression. After verifying C-erbB-2 knockout, invasion, healing, clone formation and proliferation of HEC-1A cells were assessed. Simultaneously, expression levels of the genes for P21, P27, mammalian target of rapamycin (mTOR), and Bcl-2 associated death promoter (Bad) were measured by RT-qPCR. Compared with the PTX group, CMBs significantly enhanced the absorption efficiency of PTX by HEC-1A cells. C-erbB-2 knockout had an inhibitory effect on the proliferation, migration and invasion of HEC-1A cells; cell proliferation and invasion of the group carrying PTX and plasmids simultaneously were significantly weakened. The C-erbB-2-knockout group exhibited increased expression of P21 and P27. Simultaneously loading PTX and plasmid may be novel combination therapy with great potential. C-erbB-2 may regulate the proliferation of HEC-1A cells by downregulating expression of P21 and P27.