Autophagy Inhibition Promotes Bevacizumab-induced Apoptosis and Proliferation Inhibition in Colorectal Cancer Cells
Aim: Anti-VEGF therapy plays an important role in the treatment of malignant tumors, especially metastatic malignant tumors. However, resistance and an inefficient response to anti-VEGF therapy exist. The current study aimed to investigate whether autophagy plays a part in the anti-tumor effect of bevacizumab in colorectal cancer cells. Methods: VEGF-A expression was measured by immunohistochemical methods. Cell viability and cell apoptosis were detected using 3-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT) and flow cytometry. Autophagy was assessed by a western blot, fluorescence microscopy and transmission electron microscopy. HIF-1α was measured using a western blot. A xenograft tumor model of colorectal cancer was constructed to determine the efficacy of the treatment of bevacizumab and chloroquine. Results: VEGF-A protein was upregulated in colorectal cancer tissue. Anti-VEGF (bevacizumab) inhibited cell viability and induced apoptosis. Moreover, bevacizumab induced autophagy. The inhibition of autophagy by chloroquine or by small interfering RNA promoted bevacizumab-induced apoptosis and proliferation inhibition. Further study showed that bevacizumab treatment significantly augmented HIF-1α. Furthermore, cells pretreated with YC-1, a HIF-1α inhibitor, displayed significantly attenuated bevacizumab-induced autophagy. Finally, a combinatory treatment of bevacizumab and chloroquine synergistically inhibited tumor growth in a xenograft tumor model of colorectal cancer cells. Conclusions: Our results showed that the inhibition of autophagy promoted the anti-tumor effect of bevacizumab and may offer a promising therapeutic strategy for colorectal cancer.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:9 |
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| Enthalten in: |
Journal of Cancer - 9(2018), 18 vom: 21., Seite 3407-3416 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhao, Zhi [VerfasserIn] |
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| Links: |
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| Themen: |
Anti-VEGF |
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| Anmerkungen: |
Date Revised 31.03.2024 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.7150/jca.24201 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM28907200X |
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| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a Aim: Anti-VEGF therapy plays an important role in the treatment of malignant tumors, especially metastatic malignant tumors. However, resistance and an inefficient response to anti-VEGF therapy exist. The current study aimed to investigate whether autophagy plays a part in the anti-tumor effect of bevacizumab in colorectal cancer cells. Methods: VEGF-A expression was measured by immunohistochemical methods. Cell viability and cell apoptosis were detected using 3-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT) and flow cytometry. Autophagy was assessed by a western blot, fluorescence microscopy and transmission electron microscopy. HIF-1α was measured using a western blot. A xenograft tumor model of colorectal cancer was constructed to determine the efficacy of the treatment of bevacizumab and chloroquine. Results: VEGF-A protein was upregulated in colorectal cancer tissue. Anti-VEGF (bevacizumab) inhibited cell viability and induced apoptosis. Moreover, bevacizumab induced autophagy. The inhibition of autophagy by chloroquine or by small interfering RNA promoted bevacizumab-induced apoptosis and proliferation inhibition. Further study showed that bevacizumab treatment significantly augmented HIF-1α. Furthermore, cells pretreated with YC-1, a HIF-1α inhibitor, displayed significantly attenuated bevacizumab-induced autophagy. Finally, a combinatory treatment of bevacizumab and chloroquine synergistically inhibited tumor growth in a xenograft tumor model of colorectal cancer cells. Conclusions: Our results showed that the inhibition of autophagy promoted the anti-tumor effect of bevacizumab and may offer a promising therapeutic strategy for colorectal cancer | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Anti-VEGF | |
| 650 | 4 | |a Autophagy | |
| 650 | 4 | |a Bevacizumab | |
| 650 | 4 | |a Colorectal cancer | |
| 700 | 1 | |a Xia, Guanggai |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Ni |e verfasserin |4 aut | |
| 700 | 1 | |a Su, Ruping |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Xiao |e verfasserin |4 aut | |
| 700 | 1 | |a Zhong, Li |e verfasserin |4 aut | |
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