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ABSTRACT: In the clinical setting, drug resistance remains a significant obstacle for successful chemotherapy. Bcl-2/adenovirus EIB 19-kDa-interacting protein 3 (BNIP3) is a proapoptotic member of the Bcl-2 family. To address its potential as a therapeutic target for chemosensitisation, this study investigated the effect of BNIP3 expression on chemosensitivity and reversal of oxaliplatin (L-OHP) resistance in human colon cancer cell lines. A plasmid expressing the BNIP3 gene was transfected into human parental colon cancer cell lines (SW620 and colo320) and L-OHP-resistant colon cancer cell lines (SW620/L-OHP and colo320/L-OHP) using Lipofectamine™ 2000, and the transfection efficiency was determined using fluorescence optics. Western blot analysis identified that SW620/L-OHP and colo320/L-OHP cells expressed lower levels of BNIP3 protein compared with the SW620 and colo320 cells. Transfection with the recombinant BNIP3 plasmid revealed an increase in BNIP3 expression in tumour cells. Following transfection with pDsRed-BNIP3, the chemosensitivity of parental and L-OHP-resistant cell lines to L-OHP was increased (P<0.01), as detected by the Cell Counting Kit-8 (CCK8) assay. Hoechst 33342 staining and flow cytometry revealed that the effects on L-OHP-induced apoptosis were enhanced by the overexpression of BNIP3. Chemosensitisation in human colon cancer cells was observed following treatment with the recombinant BNIP3 plasmid in vitro. The results of this study suggest that BNIP3 is a potential therapeutic target for reversing the resistance of L-OHP-resistant colon cancer cells to L-OHP.
Oncology letters 12/2012; 4(6):1195-1202. · 0.11 Impact Factor
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Hui Zeng,
Zhu Yuan,
Hong Zhu,
Lei Li,
Huashan Shi, Zi Wang,
Yu Fan,
Qian Deng,
Jianshuang Zeng,
Yinbo He,
Jianghong Xiao,
Zhiping Li
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ABSTRACT: This study aimed to transfer the hPNAS-4 gene, a novel apoptosis-related human gene, into Lewis lung cancer (LL2) and observe its radiosensitive effect on radiation therapy in vitro and in vivo.
The hPNAS-4 gene was transfected into LL2 cells, and its expression was detected via western blot. Colony formation assay and flow cytometry were used to detect the growth and apoptosis of cells treated with irradiation/PNAS-4 in vitro. The hPNAS-4 gene was transferred into LL2-bearing mice through tail vein injection of the liposome/gene complex. The tumor volumes were recorded after radiation therapy. Proliferating cell nuclear antigen (PCNA) immunohistochemistry staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay were performed to detect the tumor cell growth and apoptosis in vivo.
The hPNAS-4 gene was successfully transferred into LL2 cells and tumor tissue, and its overexpressions were confirmed via western blot analysis. Compared with the control, empty plasmid, hPNAS-4, radiation, and empty plasmid plus radiation groups, the hPNAS-4 plus radiation group more significantly inhibited growth and enhanced apoptosis of LL2 cells in vitro and in vivo (P<.05).
The hPNAS-4 gene was successfully transferred into LL2 cells and tumor tissue and was expressed in both LL2 cell and tumor tissue. The hPNAS-4 gene therapy significantly enhanced growth inhibition and apoptosis of LL2 tumor cells by radiation therapy in vitro and in vivo. Therefore, it may be a potential radiosensitive treatment of radiation therapy for lung cancer.
International journal of radiation oncology, biology, physics 07/2012; 84(4):e533-40. · 4.59 Impact Factor
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Zi Wang,
Chun-mei Huang,
Qian Deng,
Hui Zeng,
Xin Wang,
Shuang Zhang,
Feng Bi,
Qiu-lin Tang,
Ren-ming Zhong,
Ai-jun Li,
Yin-Bo He,
Ni Chen,
Zhi-ping Li,
Wei Wang
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ABSTRACT: Bcl2/adenovirus EIB 19 kDa-interacting protein 3 (BNIP3) is a proapoptotic member of the Bcl-2 family. To address its potential as a therapeutic target for radiosensitization, this study investigated the effect of Bnip3 expression on radiosensitivity of cervical cancer in vitro and in vivo.
In vitro: A plasmid expressing the BNIP3 gene was transfected into human cervical cancer HeLa cells using Lipofectamine(2000), and western blot and immunohistochemistry analysis were performed to evaluate the expression of BNIP3 in transfected cells. The effects on radiation-induced apoptosis were investigated using a clone formation assay and flow cytometry. In vivo: A total of 6 × 10⁶ HeLa cells were subcutaneously inoculated into the dorsal flank of nude mice, and plasmids expressing the BNIP3 gene were injected into the mice via the tail vein. Tumor volume was calculated, and immunohistochemistry was used to detect the expression of BNIP3 in tumor cells. TUNEL assays were performed to determine the apoptosis rates in tumor tissues.
Transfection with the recombinant BNIP3 plasmid increased expression of the Bnip3 protein in tumor cells. This apoptosis regulator significantly decreased the viability of cells (p < 0.01) and increased the apoptosis rates (p < 0.01) both in vitro and in vivo. The antitumor effect of radiotherapy was enhanced by overexpression of BNIP3, as revealed by tumor growth curve analysis.
Radiosensitization in human cervical cancer cells was observed after treatment with the recombinant BNIP3 plasmid in vitro and in vivo. Results suggested that BNIP3 may play a role in enhancement of radiotherapy efficiency, and its expression may have a synergistic effect on radiation treatments.
Cancer Biotherapy & Radiopharmaceuticals 06/2011; 26(3):279-86. · 1.44 Impact Factor
