Chemovirotherapeutic Treatment Using Camptothecin Enhances Oncolytic Measles Virus-Mediated Killing of Breast Cancer Cells

被引:20
|
作者
Tai, Chen-Jei [1 ,2 ]
Liu, Ching-Hsuan [3 ,4 ]
Pan, Yu-Chi [5 ]
Wong, Shu Hui [6 ]
Tai, Cheng-Jeng [7 ,8 ]
Richardson, Christopher D. [4 ,9 ,10 ]
Lin, Liang-Tzung [3 ,5 ]
机构
[1] Taipei Med Univ Hosp, Dept Tradit Chinese Med, Taipei, Taiwan
[2] Taipei Med Univ, Sch Med, Dept Obstet & Gynecol, Coll Med, Taipei, Taiwan
[3] Taipei Med Univ, Grad Inst Med Sci, Coll Med, Taipei, Taiwan
[4] Dalhousie Univ, Dept Microbiol & Immunol, Halifax, NS, Canada
[5] Taipei Med Univ, Sch Med, Dept Microbiol & Immunol, Coll Med, Taipei, Taiwan
[6] Taipei Med Univ, Coll Med, Int Master Program Med, Taipei, Taiwan
[7] Taipei Med Univ Hosp, Div Hematol & Oncol, Dept Internal Med, Taipei, Taiwan
[8] Taipei Med Univ, Sch Med, Dept Internal Med, Coll Med, Taipei, Taiwan
[9] Izaak Walton Killam Hlth Ctr, Dept Pediat, Halifax, NS, Canada
[10] Izaak Walton Killam Hlth Ctr, Canadian Ctr Vaccinol, Halifax, NS, Canada
关键词
VACCINE VIRUS; NECTIN-4; VIROTHERAPY; APOPTOSIS; COMBINATION; METABOLISM; EXPRESSION; IRINOTECAN; THERAPY; SYNERGY;
D O I
10.1038/s41598-019-43047-3
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Oncolytic virotherapy represents an emerging development in anticancer therapy. Although it has been tested against a variety of cancers, including breast cancer, the efficacy of oncolytic viral vectors delivered as a monotherapy is limited. Enhancing viral oncolytic therapies through combination treatment with anticancer agents is a feasible strategy. In this study, we considered a chemovirotherapeutic approach for treating breast adenocarcinoma using oncolytic measles virus (MV) and the chemotherapeutic agent camptothecin (CPT). Our results demonstrated that co-treatment of MV with CPT yielded enhanced cytotoxicity against breast cancer cells. Low dosage CPT combined with MV was also found to elicit the same therapeutic effect as high doses of CPT. At the lower dosage used, CPT did not inhibit the early stages of MV entry, nor reduce viral replication. Further studies revealed that co-treatment induced significantly enhanced apoptosis of the breast cancer cells compared to either MV or CPT alone. Overall, our findings demonstrate the potential value of MV plus CPT as a novel chemovirotherapeutic treatment against breast cancer and as a strategy to enhance MV oncolytic activity.
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页数:13
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