紫杉醇联合TLR7/8激动剂3M-052诱导小鼠结肠癌CT26细胞凋亡的研究
Paclitaxel Combined with TLR7/8 Agonist 3M-052 Inducing the Apoptosis of Mouse Colon Cancer CT26 Cells
DOI: 10.12677/WJCR.2018.84021, PDF,   
作者: 安稳定, 毛剑琴, 林 赟, 郑子瑞*:浙江海正药业股份有限公司,浙江 台州
关键词: 紫杉醇3M-052联合用药结肠癌凋亡Paclitaxel 3M-052 Drug Combination Colon Cancer Apoptosis
摘要: 目的:探讨紫杉醇联合Toll样受体7/8激动剂3M-052诱导小鼠结肠癌CT26细胞凋亡的作用及其机制。方法:使用不同浓度的3M-052和PTX联合处理CT26细胞,24 h后检测细胞活力,分析PTX与3M-052协同作用的浓度;并采用Western blot法检测CT26细胞中的Bax、Bcl-2、active-Caspase3以及cleaved-PARP I的表达情况。结果:3M-052可以明显上调小鼠PBMC分泌的TNF-α;3M-052与PTX单药或联用时均可上调Bax/Bcl-2比例,促进Caspase3活化,增强PARP I蛋白剪切,最终导致细胞凋亡。结论:3M-052或PTX单独使用均可促进CT26细胞凋亡,抑制其增殖,联用时效果更佳。
Abstract: Objective: To investigate the effect and mechanism of paclitaxel combined with Toll-like receptor 7/8 agonist 3M-052 on the apoptosis of mouse colon cancer CT26 cells. Methods: CT26 cells were treated with different concentrations of 3M-052 and PTX. The cell viability was measured after 24 h, and the synergistic concentration of PTX and 3M-052 was analyzed. The expression of Bax, Bcl-2, active-Caspase3 and cleaved-PARP I in CT26 cells were detected by Western blot. Results: 3M-052 could induce TNF-α production in mouse PBMC. Exclusive or combined use of 3M-052 and PTX could up-regulate the proportion of Bax/Bcl-2 in cells, promote the shearing of Caspase3 and PARP I protein, therefore induce cell apoptosis. Conclusion: Both 3M-052 and PTX can promote the apoptosis of CT26 cells, and inhibit its proliferation, while the effect would be better when combined.
文章引用:安稳定, 毛剑琴, 林赟, 郑子瑞. 紫杉醇联合TLR7/8激动剂3M-052诱导小鼠结肠癌CT26细胞凋亡的研究[J]. 世界肿瘤研究, 2018, 8(4): 132-138. https://doi.org/10.12677/WJCR.2018.84021

参考文献

[1] Chen, W., Zheng, R., Baade, P.D., et al. (2016) Cancer Statistics in China, 2015. CA: A Cancer Journal for Clinicians, 66, 115-132.
[Google Scholar] [CrossRef] [PubMed]
[2] Allemani, C., Matsuda, T., Di Carlo, V., et al. (2018) Global Surveillance of Trends in Cancer Survival 2000-14 (CONCORD-3): Analysis of Individual Records for 37,513,025 Patients Diagnosed with One of 18 Cancers from 322 Population-Based Registries in 71 Countries. Lancet, 391, 1023-1075.
[Google Scholar] [CrossRef
[3] Guo, X.Y., Wang, P., Du, Q.G., et al. (2015) Paclitaxel and Gemcitabine Combinational Drug-Loaded Mucoadhesive Delivery System in the Treatment of Colon Cancers. Drug Research (Stuttg), 65, 199-204.
[4] Xiong, M., Lei, Q., You, X., et al. (2017) Mannosylated Liposomes Improve Therapeutic Effects of Paclitaxel in Colon Cancer Models. Journal of Microencapsulation, 34, 513-521.
[Google Scholar] [CrossRef] [PubMed]
[5] Zhao, B.G., Vasilakos, J.P., Tross, D., et al. (2014) Combination Therapy Targeting Toll Like Receptors 7, 8 and 9 Eliminates Large Established Tumors. Journal for ImmunoTherapy of Cancer, 2, 12.
[Google Scholar] [CrossRef] [PubMed]
[6] Soriano, A.F., Helfrich, B., Chan, D.C., et al. (1999) Synergistic Effects of New Chemopreventive Agents and Conventional Cytotoxic Agents against Human Lung Cancer Cell Lines. Cancer Research, 59, 6178-6184.
[7] Xu, M., Li, M., Yang, J., et al. (2014) Adenovirus-Mediated Interleukin-24 Enhances the Inhibitory Effect of Paclitaxel on the Growth of Lung Cancer A549 Cells. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi, 30, 1150-1153.
[8] Tanimukai, H., Kanayama, D., Omi, T., et al. (2013) Paclitaxel Induces Neurotoxicity through Endoplasmic Reticulum Stress. Biochemical and Bi-ophysical Research Communications, 437, 151-155.
[Google Scholar] [CrossRef] [PubMed]
[9] Mullins, S.R., Vogel, K., Vasilakos, J.P., et al. (2017) Intratumoral Immuno-therapy with TLR7/8 Agonist MEDI9197 Modulates the Tumor Microenvironment and Holds Potential for Combination with Immune Checkpoint Inhibitors. Cancer Research, 77, 4697.
[Google Scholar] [CrossRef
[10] Porichi, O., Nikolaidou, M.E., Apostolaki, A., et al. (2009) BCL-2, BAX and P53 Expression Profiles in Endometrial Carcinoma as Studied by Real-Time PCR and Immunohistochemistry. Anticancer Research, 29, 3977-3982.