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CMBs carrying PTX and CRISPR/Cas9 targeting C‑erbB‑2 plasmids interfere with endometrial cancer cells
Siyuan Peng1, Junhong Cai2, Shan Bao3
1Department of Gynaecology and Obstetrics, Hainan Hospital Affiliated to University of South China, Haikou, Hainan 570311, P.R. China.
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.
Insights
This study shows that combining paclitaxel (PTX) with C-erbB-2 gene editing via cationic microbubbles (CMBs) inhibits endometrial cancer cell growth. This novel combination therapy shows potential for reducing side effects and improving cancer treatment.
Area of Science:
- Oncology
- Biotechnology
- Molecular Biology
Background:
- Combination therapy is crucial for reducing chemotherapy side effects and increasing drug efficacy.
- Gene editing offers a targeted approach to cancer treatment.
- Endometrial cancer cell line HEC-1A and C-erbB-2 expression are key areas of research.
Purpose of the Study:
- To investigate the combined effect of cationic microbubbles (CMBs) carrying paclitaxel (PTX) and a C-erbB-2 knockout plasmid on HEC-1A endometrial cancer cells.
- To determine the role of C-erbB-2 in regulating endometrial cancer cell function.
- To explore a novel combination therapy for endometrial cancer.
Main Methods:
- HEC-1A cells were treated with CMBs, PTX, PTX-CMBs, or CMBs carrying plasmids.
- C-erbB-2 knockout was verified using RT-qPCR and Western blotting.
- Cell proliferation, invasion, healing, and clone formation were assessed.
- Gene expression of P21, P27, mTOR, and Bad was measured by RT-qPCR.
Main Results:
- CMBs significantly enhanced PTX absorption by HEC-1A cells.
- C-erbB-2 knockout inhibited HEC-1A cell proliferation, migration, and invasion.
- Simultaneous delivery of PTX and plasmid significantly reduced cell proliferation and invasion.
- C-erbB-2 knockout led to increased expression of P21 and P27.
Conclusions:
- Simultaneously loading PTX and plasmid using CMBs represents a promising novel combination therapy for endometrial cancer.
- C-erbB-2 appears to regulate HEC-1A cell proliferation by downregulating P21 and P27 expression.
- This approach has the potential to decrease chemotherapy side effects and improve treatment utilization.
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