p53-Induced Autophagy Regulates Chemotherapy and Radiotherapy Resistance in Multidrug Resistance Cancer Cells
© The Author(s) 2021..
BACKGROUND: Multidrug resistance (MDR), a major problem in oncology therapy, limits the effectiveness of anticancer drugs. Although p53 functions as a tumor suppressor, the associations between p53 status, autophagy, and MDR are complicated and conditional.
METHOD: In this report, p53-null human ovarian cancer cell line SKOV3 and its MDR phenotype SKVCR and human leukemia cell line CEM and its MDR phenotype CEM-VLB) (p53 mutant cell line) were used.
RESULTS: Compared to parental SKOV3, the mRNA and protein levels of MAPLC3-II and Beclin1 were higher in SKVCR cells. The inhibition of autophagy by 3-MA significantly sensitized SKVCR to VCR. Conversely, in drug-resistant leukemic cells CEM-VLB, the expressions of Beclin1 and MAPLC3-II were lower than CEM. CEM and CEM-VLB cells were treated with VLB .01 or 0.5 μg/mL, respectively, and the expression of p53 and autophagy up-regulated after VLB (.01 μg/mL) treatment in CEM cells. The percentage of S-phase and G2/M phase cells up-regulated significantly by .01 μg/mL VLB in CEM, which may relate to the status of p53 of CEM cells. A combination of radiation with 3-MA significantly increased apoptosis in CEM-VLB cells.
CONCLUSION: Our discovery found that p53 is an important regulator controlling the balance between autophagy and MDR, as a potential drug target for ovarian cancer and leukemia.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:19 |
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| Enthalten in: |
Dose-response : a publication of International Hormesis Society - 19(2021), 4 vom: 11. Okt., Seite 15593258211048046 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ma, Shumei [VerfasserIn] |
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| Links: |
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| Themen: |
Acute lymphocytic leukemia |
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| Anmerkungen: |
Date Revised 27.04.2022 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1177/15593258211048046 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
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| 520 | |a © The Author(s) 2021. | ||
| 520 | |a BACKGROUND: Multidrug resistance (MDR), a major problem in oncology therapy, limits the effectiveness of anticancer drugs. Although p53 functions as a tumor suppressor, the associations between p53 status, autophagy, and MDR are complicated and conditional | ||
| 520 | |a METHOD: In this report, p53-null human ovarian cancer cell line SKOV3 and its MDR phenotype SKVCR and human leukemia cell line CEM and its MDR phenotype CEM-VLB) (p53 mutant cell line) were used | ||
| 520 | |a RESULTS: Compared to parental SKOV3, the mRNA and protein levels of MAPLC3-II and Beclin1 were higher in SKVCR cells. The inhibition of autophagy by 3-MA significantly sensitized SKVCR to VCR. Conversely, in drug-resistant leukemic cells CEM-VLB, the expressions of Beclin1 and MAPLC3-II were lower than CEM. CEM and CEM-VLB cells were treated with VLB .01 or 0.5 μg/mL, respectively, and the expression of p53 and autophagy up-regulated after VLB (.01 μg/mL) treatment in CEM cells. The percentage of S-phase and G2/M phase cells up-regulated significantly by .01 μg/mL VLB in CEM, which may relate to the status of p53 of CEM cells. A combination of radiation with 3-MA significantly increased apoptosis in CEM-VLB cells | ||
| 520 | |a CONCLUSION: Our discovery found that p53 is an important regulator controlling the balance between autophagy and MDR, as a potential drug target for ovarian cancer and leukemia | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a acute lymphocytic leukemia | |
| 650 | 4 | |a autophagy | |
| 650 | 4 | |a ionizing radiation | |
| 650 | 4 | |a multidrug resistance | |
| 650 | 4 | |a ovarian cancer | |
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| 700 | 1 | |a Liu, Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Xue, Chang |e verfasserin |4 aut | |
| 700 | 1 | |a Tian, Zhujun |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Lan |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Xiaodong |e verfasserin |4 aut | |
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