scholarly journals p53-Induced Autophagy Regulates Chemotherapy and Radiotherapy Resistance in Multidrug Resistance Cancer Cells

Dose-Response ◽  
2021 ◽  
Vol 19 (4) ◽  
pp. 155932582110480
Author(s):  
Shumei Ma ◽  
Dejuan Kong ◽  
Xinxin Fu ◽  
Lin Liu ◽  
Yi Liu ◽  
...  

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.

2021 ◽  
Vol 11 ◽  
Author(s):  
Jing-Quan Wang ◽  
Zhuo-Xun Wu ◽  
Yuqi Yang ◽  
Jin-Sui Li ◽  
Dong-Hua Yang ◽  
...  

Ovarian cancer is one of the leading female malignancies which accounts for the highest mortality rate among gynecologic cancers. Surgical cytoreduction followed by chemotherapy is the mainstay of treatment. However, patients with recurrent ovarian cancer are likely to exhibit resistance to chemotherapy due to reduced sensitivity to chemotherapeutic drugs. Adenosine triphosphate (ATP)-binding cassette (ABC) transporters have been extensively studied as multidrug resistance (MDR) mediators since they are responsible for the efflux of various anticancer drugs. Multidrug resistance protein 7 (MRP7, or ABCC10) was discovered in 2001 and revealed to transport chemotherapeutic drugs. Till now, only limited knowledge was obtained regarding its roles in ovarian cancer. In this study, we established an MRP7-overexpressing ovarian cancer cell line SKOV3/MRP7 via transfecting recombinant MRP7 plasmids. The SKOV3/MRP7 cell line was resistant to multiple anticancer drugs including paclitaxel, docetaxel, vincristine and vinorelbine with a maximum of 8-fold resistance. Biological function of MRP7 protein was further determined by efflux-accumulation assays. Additionally, MTT results showed that the drug resistance of the SKOV3/MRP7 cells was reversed by cepharanthine, a known inhibitor of MRP7. Moreover, we also found that the overexpression of MRP7 enhanced the migration and epithelial-mesenchymal transition (EMT) induction. In conclusion, we established an in vitro model of MDR in ovarian cancer and suggested MRP7 overexpression as the leading mechanism of chemoresistance in this cell line. Our results demonstrated the potential relationship between MRP7 and ovarian cancer MDR.


2013 ◽  
Vol 14 (9) ◽  
pp. 4983-4988 ◽  
Author(s):  
Ning-Ning Wang ◽  
Li-Jun Zhao ◽  
Li-Nan Wu ◽  
Ming-Feng He ◽  
Jun-Wei Qu ◽  
...  

Author(s):  
Rahul Kumar Gupta ◽  
Renu Bharat Rathi

Background: In the last few decades, plants have been playing a vital role in treating cancer and infectious diseases. Natural products have been rediscovered as effective methods of drug production amid advances in combinatorial chemistry. Roots of Martynia annua are being used as a folklore remedy for the treatment of cancer and rheumatism successfully. Aims of the Study: In the present study, ethanolic, aqueous and hydro-ethanolic root extracts of Martynia annua were screened for in vitro cytotoxicity activity using different cell lines. Settings and Design: In the experiment, lung cancer cell lines (A549), leukemia cancer cell lines (K562), oral cancer cell lines (SCC-40), breast cancer cell lines (MCF-7) & cervix cancer cell lines (SiHa) were studied on the extracts. Materials and Methods: The method used was Sulforhodamine B (SRB) assay technique in which growth inhibition of 50% (GI50) was analyzed by comparing it with standard drug Adriamycin (ADR) (doxorubicin). Results: Aqueous & ethanolic extract of Martynia annua root had shown high anticancer activity with GI50 value 11.3µg/ml and 20.4µg/ml respectively on human leukemia cell line K-562 but for human breast cancer cell line MCF-7, human lung cancer cell line A-549, human squamous cell carcinoma SCC-40 and human cervical cancer cell line SiHa the extracts showed activity in more than 80µg/ml. Conclusion: The anticancer activity of aqueous extract of Martynia annua root was found superior than the ethanolic extract in Human Leukemia Cell Line K-562. The study indicates that the Martynia annua root extracts are most effective against the fast proliferative cells (Leukemic cells) and possibly a cell cycle arrest (needed to be proved as future perspective) is the mode of action of the extract. To study its effect on targeted cancers, specific in vivo scientific studies and clinical trials should be carried out by further researchers.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4828-4828
Author(s):  
Bao-An Chen ◽  
Xue-Yun Shan ◽  
Jian Cheng ◽  
Feng Gao ◽  
Jia-Hua Ding ◽  
...  

Abstract Abstract 4828 Objective This study was aimed to investigate the reversible effect of tyrosine kinase inhibitors(TKI)on Multidrug resistance cell line K562/A02. Methods The expression levels of mdr-1 mRNA and bcr-abl mRNA were assayed by RT-PCR. The protein levels of P-glycoprotein (P-gp) and P210 were detected by Western blot. The DNR accumulation of K562/A02 cells were analyzed by flow cytometry (FCM). Results Analysis of the inhibition rate showed that 0.0625μmol/L Imatinib or 5nM Nilotinib alone had no effect on the inhibition of K562/A02 cells. The fluorescence intensity of intracellular DNR of Imatinib, Nilotinib in K562/A02 cells was 7.85%, 12.02% (respectively of that in K562 cells). Imatinib or Nilotonib alone could decrease the mdr-1 mRNA and bcr-abl mRNA expression levels (Imatinib 0.65±0.02, 0.87±0.02; Nilotinib 0.48±0.04, 0.73 ±0.02) respectively, all these of which were significantly lower than the K562/A02 cells group 0.96±0.01, 1.87±0.04. The P-gp and P210 protein expression levels were also down after treated with different drugs (Imatinib 0.74±0.02, 0.68±0.01; Nilotinib 0.61±0.05, 0.60±0.01; the K562/A02 cells group 0.93±0.01, 1.25±0.03). Conclusion It is concluded that multidrug resistance (MDR) can be partially reversed by Imatinib or Nilotinib. The effect of Nilotinib was greater than Imatinib. Disclosures No relevant conflicts of interest to declare.


2012 ◽  
Vol 535-537 ◽  
pp. 2420-2424 ◽  
Author(s):  
Shu Li Shao ◽  
Wei Wei Zhang ◽  
Wei Zhao ◽  
Guang Hui Wu

To observe the effects of hydroxycamptothecine(HCPT) on the growth and apoptosis of gastric cancer cell line. The viability of human leukemia cell line K562 was determined by MTT, cell morphology was observed under AO staining and electron microscopy, the apoptosis was measured using flow cytometry analysis. The results indicated that the growth of human leukemia cell line K562 was significantly inhibited by HCPT, and the IC50 was 8.0µg/mL. Morphological variations of apoptosis were observed at 48 hours treated with HCPT by AO staining and apoptosis body was observed under electron microscope. The results indicated that HCPT can suppress the growth of human leukemia cell line K562 and induce apoptosis of the cells.


Author(s):  
Shadi Mahdizadeh ◽  
Gholamreza Karimi ◽  
Javad Behravan ◽  
Sepideh Arabzadeh ◽  
Hermann Lage ◽  
...  

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