An oncolytic adenovirus expressing interleukin-24 enhances antitumor activities in combination with paclitaxel in breast cancer cells.
An oncolytic adenovirus expressing interleukin-24 enhances antitumor activities in combination with paclitaxel in breast cancer cells.
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DOI：
10.3892/mmr.2013.1680
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发表时间：
2013-11
影响因子：
3.4
通讯作者：
Lin Fang;Qian Cheng;J. Bai;Ying Qi;Jun-jie Liu;Liantao Li;Junnian Zheng
中科院分区：
文献类型：
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作者：
Lin Fang;Qian Cheng;J. Bai;Ying Qi;Jun-jie Liu;Liantao Li;Junnian Zheng
溶瘤腺病毒是一类新型的抗癌治疗，基于它们在恶性细胞内选择性复制导致细胞溶解的能力。复制选择性腺病毒ZD 55-IL-24是通过携带E1 B-55 kDa缺失并与白细胞介素-24（IL-24）武装而构建的。微管稳定药物紫杉醇（PTX）在复发性癌症中表现出活性。在本研究中，研究了PTX和ZD 55-IL-24联合对乳腺癌细胞的协同抗肿瘤作用。结果表明，PTX在转基因mRNA和蛋白表达中具有不同的作用。ZD 55-IL-24联合PTX可明显抑制MDA-MB-231和Bcap-37细胞的生长。PTX增加了病毒的摄取，似乎没有改变乳腺癌细胞中ZD 55-IL-24的复制。Annexin V-异硫氰酸荧光素/碘化丙啶染色和Hoechst 33258试验表明，当与PTX联合给药时，ZD 55-IL-24诱导凋亡细胞数量增加。研究表明，ZD 55-IL-24与PTX结合高度共存，增加了促凋亡蛋白水平，激活了caspase-3，-7和-9，并下调了抗凋亡蛋白。这些结果表明，ZD 55-IL-24与PTX组合在乳腺癌细胞中表现出显著增加的细胞毒性和凋亡诱导作用。因此，这种化学基因病毒治疗策略被证明上级传统的化疗或单独的基因病毒治疗。
Oncolytic adenoviruses are a novel class of anticancer treatment, based upon their ability to replicate selectively within malignant cells resulting in cell lysis. The replication‑selective adenovirus, ZD55‑IL‑24, was constructed by harboring an E1B‑55 kDa deletion and arming with interleukin-24 (IL-24). The microtubule‑stabilizing drug paclitaxel (PTX) exhibits activity in relapsed cancer. In the present study, the synergistic antitumor effects of the combination of PTX and ZD55‑IL‑24 on breast cancer cells was investigated. The results demonstrated that there were different roles for PTX in the expression of transgenic mRNA and protein. ZD55‑IL‑24 combined with PTX induced marked growth inhibition of MDA‑MB‑231 and Bcap‑37 cells. PTX increased viral uptake and appeared not to alter the replication of ZD55‑IL‑24 in breast cancer cells. Annexin V‑fluorescein isothiocyanate/propidium iodide staining and the Hoechst 33258 assay indicated that ZD55‑IL‑24 induced an increase in the number of apoptotic cells when administered in combination with PTX. It was demonstrated that ZD55‑IL‑24 conjugated with PTX was highly concomitant, and increased proapoptotic proteins levels, activated caspase‑3, -7 and -9 and downregulated anti‑apoptotic proteins. These results suggested that ZD55‑IL‑24 in combination with PTX exhibited a markedly increased cytotoxic and apoptosis‑inducing effect in breast cancer cells. Thus, this chemo‑gene‑viro therapeutic strategy was demonstrated to be superior to conventional chemotherapy or gene‑viro therapy alone.