4.5 Article

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

期刊

MOLECULAR MEDICINE REPORTS
卷 24, 期 6, 页码 -

出版社

SPANDIDOS PUBL LTD
DOI: 10.3892/mmr.2021.12470

关键词

chemotherapy-gene combination therapy; chemotherapy drug; gene editing; tumor therapy; ultrasound cationic microbubbles

资金

  1. Hainan Key Program of Research and Development [ZDYF2019123]

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The study investigated the effect of CMBs carrying PTX and C-erbB-2 knockout plasmid on endometrial cancer cells, revealing that C-erbB-2 knockout inhibits proliferation, migration, and invasion of HEC-1A cells. Loading PTX and plasmid simultaneously may be a novel combination therapy with great potential. C-erbB-2 may regulate cell proliferation by downregulating expression of P21 and P27 in HEC-1A cells.
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.

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