Co-Delivery of Paclitaxel and shMCL-1 by Folic Acid-Modified Nonviral Vector to Overcome Cancer Chemotherapy Resistance
| Autor: | Jing Chen, Wen Nie, Zhiyong Qian, Xiaoxiao Liu, Junming Miao, Tingting Yang, Bilan Wang, Xiang Gao, Ting Yu, Yunzhu Lin, Xiao Liang, Xue Mi, Mengni Ran, Zehuo Hong |
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| Rok vydání: | 2021 |
| Předmět: |
Cancer chemotherapy
Paclitaxel Mice Nude Apoptosis Transfection Nanocomposites chemistry.chemical_compound Mice Folic Acid Cell Line Tumor Neoplasms Medicine Animals Humans General Materials Science Vector (molecular biology) RNA Small Interfering bcl-2-Associated X Protein Co delivery Drug Carriers business.industry Cancer General Chemistry medicine.disease Antineoplastic Agents Phytogenic G2 Phase Cell Cycle Checkpoints chemistry Folic acid Proto-Oncogene Proteins c-bcl-2 Drug Resistance Neoplasm Cancer research Myeloid Cell Leukemia Sequence 1 Protein business Chemotherapy resistance Signal Transduction |
| Zdroj: | Small methods. 5(5) |
| ISSN: | 2366-9608 |
| Popis: | Acquired chemoresistance presents a major clinical impediment, which is an urgent problem to be solved. Interestingly, myeloma cell leukemia-1 (MCL-1) and folate receptor expression levels are higher in chemotherapy-resistant patients than in pretreatment patients. In this study, a multifunctional folic acid (FA)-targeting core-shell structure is presented for simultaneous delivery of shMCL-1 and paclitaxel (PTX). The transfection efficiency of shMCL-1 with the FA-targeting delivery system is higher than with a nontargeting delivery system in Skov3 and A2780T cells. The FA-targeting system significantly inhibits cell growth, blocks cell cycles, and promotes apoptosis of cancer cells in vitro. The mechanisms involved in inhibiting growth are related to Bcl-2/Bax and cdc2/Cyclin B1 pathways. An analysis of RNA sequencing suggests that shMCL-1 reverses chemoresistance through regulating genes such as regulator of chromosome condensation 2 (RCC2). The synergetic effect of shMCL-1 and PTX effectively inhibits tumor growth in both PTX-resistant and normal cancer models by inducing tumor apoptosis, inhibiting proliferation, and limiting tumor angiogenesis. The study results indicate that a FA-targeting delivery system combining shMCL-1 with PTX can simultaneously target tumor sites and restore the sensitivity of chemotherapy-resistant cancer to PTX. These findings have important implications for patients with normal or PTX-resistant cancer. |
| Databáze: | OpenAIRE |
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