Anti-tumor Synergistic Effect of a Dual Cancer-Specific Recombinant Adenovirus and Paclitaxel on Breast Cancer

This study aimed at investigating the anticancer potential of the recombinant adenovirus Ad-apoptin-hTERTp-E1a (Ad-VT) and its synergistic combination with paclitaxel (PTX) in breast cancer treatment. First, we used the Calcusyn software to analyze the synergy between the Ad-VT and paclitaxel, and t...

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Main Authors: Jing Wang, Yiquan Li, Shanzhi Li, Wei Yao, Xing Liu, Yilong Zhu, Wenjie Li, Liankun Sun, Ningyi Jin, Xiao Li
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-03-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fonc.2020.00244/full
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author Jing Wang
Yiquan Li
Yiquan Li
Shanzhi Li
Shanzhi Li
Wei Yao
Xing Liu
Xing Liu
Yilong Zhu
Yilong Zhu
Wenjie Li
Wenjie Li
Liankun Sun
Ningyi Jin
Ningyi Jin
Ningyi Jin
Xiao Li
Xiao Li
Xiao Li
author_facet Jing Wang
Yiquan Li
Yiquan Li
Shanzhi Li
Shanzhi Li
Wei Yao
Xing Liu
Xing Liu
Yilong Zhu
Yilong Zhu
Wenjie Li
Wenjie Li
Liankun Sun
Ningyi Jin
Ningyi Jin
Ningyi Jin
Xiao Li
Xiao Li
Xiao Li
author_sort Jing Wang
collection DOAJ
description This study aimed at investigating the anticancer potential of the recombinant adenovirus Ad-apoptin-hTERTp-E1a (Ad-VT) and its synergistic combination with paclitaxel (PTX) in breast cancer treatment. First, we used the Calcusyn software to analyze the synergy between the Ad-VT and paclitaxel, and to determine the final drug concentration. Second, we used crystal violet staining and WST-1 assays to analyze the inhibitory effect of Ad-VT and paclitaxel combination treatment on MCF-7, MDA-MB-231, and MCF-10A cells. Subsequently, we used Hoechst, Annexin V, JC-1 staining to analyze the inhibition pathway of drugs on breast cancer cells. We also used Transwell assays to analyze the cell migration and invasion of MCF-7 and MDA-MB-231 cells. The pGL4.51 plasmid was used to transfect and to generate MDA-MB-231 cells, that stably express luciferase (MDA-MB-231-LUC). The in vivo tumor inhibition effect of Ad-VT and paclitaxel combination treatment was subsequently confirmed using a tumor-bearing nude mouse model. This combination treatment can increase the inhibition of breast cancer cells and reduce paclitaxel toxicity. Ad-VT had a strong apoptosis-inducing effect on MCF-7 and MDA-MB-231 cells, that was mainly mediated through the mitochondrial apoptotic pathway. The combination of Ad-VT and paclitaxel could significantly increase the inhibition of breast cancer cell migration and invasion. Combination of Ad-VT and paclitaxel can inhibit tumor growth and reduce toxicity in vivo. Ad-VT can also inhibit the growth of breast cancer cells and promote their apoptosis. Meanwhile, when it is combined with paclitaxel, Ad-VT could play a significant role in a synergistic tumor inhibition.
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spelling doaj.art-3d4f8b2fbb3a4141a19b255f6862ae8d2022-12-21T19:56:36ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-03-011010.3389/fonc.2020.00244510374Anti-tumor Synergistic Effect of a Dual Cancer-Specific Recombinant Adenovirus and Paclitaxel on Breast CancerJing Wang0Yiquan Li1Yiquan Li2Shanzhi Li3Shanzhi Li4Wei Yao5Xing Liu6Xing Liu7Yilong Zhu8Yilong Zhu9Wenjie Li10Wenjie Li11Liankun Sun12Ningyi Jin13Ningyi Jin14Ningyi Jin15Xiao Li16Xiao Li17Xiao Li18Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, ChinaInstitute of Military Veterinary Medicine, Academy of Military Medical Science, Changchun, ChinaAcademician Workstation of Jilin Province, Changchun University of Chinese Medicine, Changchun, ChinaInstitute of Military Veterinary Medicine, Academy of Military Medical Science, Changchun, ChinaAcademician Workstation of Jilin Province, Changchun University of Chinese Medicine, Changchun, ChinaCenter for Disease Control and Prevention, Agency for Offices Administration, Central Military Commission, Beijing, ChinaAcademician Workstation of Jilin Province, Changchun University of Chinese Medicine, Changchun, ChinaDepartment of Thoracic Surgery, The First Hospital of Jilin University, Changchun, ChinaInstitute of Military Veterinary Medicine, Academy of Military Medical Science, Changchun, ChinaAcademician Workstation of Jilin Province, Changchun University of Chinese Medicine, Changchun, ChinaInstitute of Military Veterinary Medicine, Academy of Military Medical Science, Changchun, ChinaAcademician Workstation of Jilin Province, Changchun University of Chinese Medicine, Changchun, ChinaDepartment of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, ChinaInstitute of Military Veterinary Medicine, Academy of Military Medical Science, Changchun, ChinaAcademician Workstation of Jilin Province, Changchun University of Chinese Medicine, Changchun, ChinaJiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, ChinaInstitute of Military Veterinary Medicine, Academy of Military Medical Science, Changchun, ChinaAcademician Workstation of Jilin Province, Changchun University of Chinese Medicine, Changchun, ChinaJiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, ChinaThis study aimed at investigating the anticancer potential of the recombinant adenovirus Ad-apoptin-hTERTp-E1a (Ad-VT) and its synergistic combination with paclitaxel (PTX) in breast cancer treatment. First, we used the Calcusyn software to analyze the synergy between the Ad-VT and paclitaxel, and to determine the final drug concentration. Second, we used crystal violet staining and WST-1 assays to analyze the inhibitory effect of Ad-VT and paclitaxel combination treatment on MCF-7, MDA-MB-231, and MCF-10A cells. Subsequently, we used Hoechst, Annexin V, JC-1 staining to analyze the inhibition pathway of drugs on breast cancer cells. We also used Transwell assays to analyze the cell migration and invasion of MCF-7 and MDA-MB-231 cells. The pGL4.51 plasmid was used to transfect and to generate MDA-MB-231 cells, that stably express luciferase (MDA-MB-231-LUC). The in vivo tumor inhibition effect of Ad-VT and paclitaxel combination treatment was subsequently confirmed using a tumor-bearing nude mouse model. This combination treatment can increase the inhibition of breast cancer cells and reduce paclitaxel toxicity. Ad-VT had a strong apoptosis-inducing effect on MCF-7 and MDA-MB-231 cells, that was mainly mediated through the mitochondrial apoptotic pathway. The combination of Ad-VT and paclitaxel could significantly increase the inhibition of breast cancer cell migration and invasion. Combination of Ad-VT and paclitaxel can inhibit tumor growth and reduce toxicity in vivo. Ad-VT can also inhibit the growth of breast cancer cells and promote their apoptosis. Meanwhile, when it is combined with paclitaxel, Ad-VT could play a significant role in a synergistic tumor inhibition.https://www.frontiersin.org/article/10.3389/fonc.2020.00244/fullrecombinant adenoviruspaclitaxeltoxicitysynergybreast cancer
spellingShingle Jing Wang
Yiquan Li
Yiquan Li
Shanzhi Li
Shanzhi Li
Wei Yao
Xing Liu
Xing Liu
Yilong Zhu
Yilong Zhu
Wenjie Li
Wenjie Li
Liankun Sun
Ningyi Jin
Ningyi Jin
Ningyi Jin
Xiao Li
Xiao Li
Xiao Li
Anti-tumor Synergistic Effect of a Dual Cancer-Specific Recombinant Adenovirus and Paclitaxel on Breast Cancer
Frontiers in Oncology
recombinant adenovirus
paclitaxel
toxicity
synergy
breast cancer
title Anti-tumor Synergistic Effect of a Dual Cancer-Specific Recombinant Adenovirus and Paclitaxel on Breast Cancer
title_full Anti-tumor Synergistic Effect of a Dual Cancer-Specific Recombinant Adenovirus and Paclitaxel on Breast Cancer
title_fullStr Anti-tumor Synergistic Effect of a Dual Cancer-Specific Recombinant Adenovirus and Paclitaxel on Breast Cancer
title_full_unstemmed Anti-tumor Synergistic Effect of a Dual Cancer-Specific Recombinant Adenovirus and Paclitaxel on Breast Cancer
title_short Anti-tumor Synergistic Effect of a Dual Cancer-Specific Recombinant Adenovirus and Paclitaxel on Breast Cancer
title_sort anti tumor synergistic effect of a dual cancer specific recombinant adenovirus and paclitaxel on breast cancer
topic recombinant adenovirus
paclitaxel
toxicity
synergy
breast cancer
url https://www.frontiersin.org/article/10.3389/fonc.2020.00244/full
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