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Published on: June 15, 2016
[Small interfering RNA targeting STAT3 enhances antitumor activity of doxorubicin]
Tian-Xiao Wang1, Ying-Ying Wang, Zhong-Qing Zhang
1Institute of Chinese Materia Medica, College of Pharmacy, Henan University, Kaifeng 475004, China. wtx1975@126.com
Abstract:
This study is to investigate the effect of small interfering RNA targeting STAT3 (STAT3-siRNA) enhancing antitumor activity of doxorubicin. RT-PCR and Western blotting were used to test the expression of STAT3 mRNA and protein in the HepG2, HeLa and K562/DOX cells and the effect of STAT3-siRNA on the expression of STAT3 mRNA and protein. MTT and Trypan blue assay were performed to determine the inhibitory effect of STAT3-siRNA on HepG2, HeLa and K562/DOX cells and the effect of STAT3-siRNA enhancing antitumor activity of doxorubicin. The effects of STAT3-siRNA on intracellular accumulation of doxorubicin and cell apoptosis were performed by Arrary Scan V(TI)HCS600 High-Contents. The results showed that STAT3 gene, STAT3 and pSTAT3 protein were highly expressed in HepG2, HeLa and K562/DOX cells and STAT3-siRNA decreased the expression of STAT3 mRNA and protein. STAT3-siRNA inhibited the growth of HepG2, HeLa and K562/DOX cells. STAT3-siRNA in combination with doxorubicin decreased by 3.13, 5.22 and 1.74 fold of IC50 of HepG2, HeLa and K562/DOX cells compared with doxorubicin only. Intracellular accumulation of doxorubicin increased by 16.8%, 12.87% and 25.67% respectively in HepG2, HeLa and K562/DOX cells in the presence of STAT3-siRNA. An enhancement of doxorubicin-induced cell apoptosis was observed in HepG2, HeLa and K562/DOX cells treated with STAT3-siRNA. The results suggested that STAT3-siRNA could enhance the antitumor activity of doxorubicin on HepG2, HeLa and K562/DOX cells.
Insights
Small interfering RNA targeting STAT3 (STAT3-siRNA) enhances doxorubicin's antitumor activity by reducing STAT3 expression and increasing drug accumulation. This combination therapy boosts doxorubicin-induced apoptosis in cancer cells.
Area of Science:
- Molecular Biology
- Cancer Research
- Pharmacology
Context:
- Signal transducer and activator of transcription 3 (STAT3) is frequently overexpressed in various cancers, contributing to tumor growth and drug resistance.
- Doxorubicin is a widely used chemotherapy agent, but its efficacy can be limited by resistance mechanisms.
- STAT3 signaling plays a role in cellular resistance to chemotherapy, including doxorubicin.
Purpose:
- To investigate the synergistic effect of STAT3-siRNA and doxorubicin on cancer cells.
- To evaluate how STAT3-siRNA affects doxorubicin uptake and apoptosis.
- To determine if STAT3 inhibition can overcome doxorubicin resistance.
Summary:
- STAT3-siRNA effectively reduced STAT3 mRNA and protein expression in HepG2, HeLa, and K562/DOX cells.
- Combined treatment with STAT3-siRNA and doxorubicin significantly decreased the IC50 values compared to doxorubicin alone.
- STAT3-siRNA enhanced intracellular doxorubicin accumulation and promoted doxorubicin-induced apoptosis in the tested cancer cell lines.
Impact:
- STAT3-siRNA demonstrates potential as an adjuvant therapy to enhance the efficacy of doxorubicin in cancer treatment.
- This approach may offer a strategy to overcome or circumvent chemotherapy resistance.
- Further research could explore the clinical translation of STAT3-targeted therapies in combination with conventional chemotherapeutics.
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