p53-Induced Autophagy Regulates Chemotherapy and Radiotherapy Resistance in Multidrug Resistance Cancer Cells.
p53-Induced Autophagy Regulates Chemotherapy and Radiotherapy Resistance in Multidrug Resistance Cancer Cells.
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p53 诱导的自噬调节多药耐药癌细胞的化疗和放疗耐药性
DOI：
10.1177/15593258211048046
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发表时间：
2021-10
期刊：
影响因子：
--
通讯作者：
Liu X
中科院分区：
文献类型：
--
作者：
Ma S;Kong D;Fu X;Liu L;Liu Y;Xue C;Tian Z;Li L;Liu X
多药耐药（MDR）是肿瘤治疗中的一个主要问题，它限制了抗癌药物的有效性。尽管p53作为肿瘤抑制因子发挥作用，但p53状态、自噬和MDR之间的关联是复杂且有条件的。方法采用p53基因缺失的人卵巢癌细胞系SKOV3及其MDR表型SKVCR和人白血病细胞系CEM及其MDR表型CEM- vlb （p53突变细胞系）。结果与亲本SKOV3相比，SKVCR细胞中MAPLC3-II和Beclin1的mRNA和蛋白表达水平较高。3-MA对自噬的抑制使SKVCR对VCR显着增敏。相反，在耐药白血病细胞CEM- vlb中，Beclin1和MAPLC3-II的表达低于CEM。用VLB处理CEM和CEM-VLB细胞。分别为0.01或0.5 μg/mL，且VLB后p53和自噬的表达上调。0.01 μg/mL)处理。s期和G2/M期细胞比例显著上调。1 μg/mL VLB在CEM中表达，可能与CEM细胞p53状态有关。放射联合3-MA显著增加了CEM-VLB细胞的凋亡。结论我们的发现发现p53是控制自噬与耐多药之间平衡的重要调节因子，是卵巢癌和白血病的潜在药物靶点。
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.
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影响因子：
4.2
作者：
Cui, Li;Song, Zhiheng;Liu, Xiaodong
通讯作者：
Liu, Xiaodong
影响因子：
5.1
作者：
Kim, Won Kyung;Pyee, Yuna;Lee, Sang Kook
通讯作者：
Lee, Sang Kook
miR-23b-3p通过靶向ATG12和HMGB2调节胃癌细胞的化疗耐药
影响因子：
9
作者：
An Y;Zhang Z;Shang Y;Jiang X;Dong J;Yu P;Nie Y;Zhao Q
通讯作者：
Zhao Q
影响因子：
12.4
作者：
Mrschtik M;O'Prey J;Lao LY;Long JS;Beaumatin F;Strachan D;O'Prey M;Skommer J;Ryan KM
通讯作者：
Ryan KM
影响因子：
64.8
作者：
Green, Douglas R.;Kroemer, Guido
通讯作者：
Kroemer, Guido