Objective: To achieve a reversal of multidrug resistance (MDR) in cancer chemotherapy, it is crucial to clarify the characteristics of MDR cells generated by various types of chemotherapeutic agents and to find novel targets.
Methods: Cisplatin- and paclitaxel-resistant HeLa sublines (HeLa/CDDP and HeLa/TXL, respectively) were established by continuous exposure and their cellular changes were examined based on growth inhibition assays, the transport activity of P-glycoprotein/MDR1, and a RT-PCR analysis of MDR-related factors.
Results: HeLa/CDDP cells showed cross-resistance to platinum derivatives, whereas HeLa/TXL cells were resistant to a variety of MDR1 substrates. Transport activity of MDR1 was reduced in HeLa/CDDP cells and the expression of MDR1 was significantly accelerated in HeLa/TXL cells, compared with HeLa cells. In addition, the expression levels of MDR-related transporters (MRP1-5 or BCRP), betatubulin which is a target for taxanes, and apoptosis-regulated factors were comparable among the three cell lines. On the other hand, the mRNA levels of gamma-glutamyl transferase, but not gamma-glutamyl cysteine synthetase, were higher in HeLa/CDDP cells than in HeLa and HeLa/TXL cells.
Conclusions: HeLa/CDDP cells showed decreased activity and expression of MDR1 and overexpression of gamma-GT but not gamma-GCS whereas the activity of MDR1 in HeLa/TXL cells was significantly enhanced. Thus, the molecular changes to HeLa cells caused by continuous exposure to cisplatin or paclitaxel were in part clarified, and therefore an understanding of the cellular changes induced by chemotherapeutic agents will be necessary to establish a strategy for reversing MDR.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s00280-006-0226-5 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The new-generation proteasome inhibitor oprozomib increases the sensitivity of cervical cancer cells to cisplatin-induced apoptosis.
J Biol Regul Homeost Agents
May 2021
Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
This study aimed to evaluate the anti-tumor effect of a new generation of protease inhibitor, oprozomib (OPZ), used alone and in combination with cisplatin, also called CDDP, on cervical cancer. Five different types of cervical cancer cell lines - HeLa, Caski, HeLa-CDDP, C33a, and SiHa - and one nontransformed cervical cell line - HaCaT -were treated with OPZ alone or in combination with cisplatin. The inhibitory effects of OPZ and cisplatin on the proliferation of cervical cancer cells were then analyzed using cytotoxicity tests, flow cytometry, and Western blotting.
View Article and Find Full Text PDFReduction-sensitive platinum (IV)-prodrug nano-sensitizer with an ultra-high drug loading for efficient chemo-radiotherapy of Pt-resistant cervical cancer in vivo.
J Control Release
October 2020
State Key Laboratory of Organic-Inorganic Composite Materials, Beijing University of Chemical Technology, Beijing 100029, China; Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029, China; Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, China; College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China; Key Laboratory of Biomedical Materials of Natural Macromolecules (Beijing University of Chemical Technology), Ministry of Education, Beijing 100029, China. Electronic address:
Cisplatin is widely used in the chemoradiotherapy (CRT) of cervical cancers. However, despite the severe systemic side effects, the therapeutic efficacy of cisplatin is often compromised by the development of drug resistance, which is closely related to the elevated intracellular thiol-containing species (especially glutathione (GSH)) and the adenosine triphosphate (ATP)-dependent glutathione S-conjugate pumps. The construction of a safe and redox-sensitive nano-sensitizer with high disulfide density and high Pt(IV) prodrug loading capacity (up to 16.
View Article and Find Full Text PDFmiR-205 Promotes Apoptosis of Cervical Cancer Cells and Enhances Drug Sensitivity of Cisplatin by Inhibiting YAP1.
Cancer Biother Radiopharm
June 2020
Department of Pharmacology, Qiqihar Medical University, Qiqihar, China.
Elevated expression of Yes-associated protein (YAP1) involves in the pathogenesis of cervical cancer. Bioinformatics analysis showed a targeting relationship between miR-205 and the 3'-UTR of YAP1. In this study, we aim to explore the role of miR-205 in the proliferation, apoptosis, or cisplatin (CDDP) resistance of cervical cancer cells.
View Article and Find Full Text PDFmiR-144 reverses cisplatin resistance in cervical cancer via targeting LHX2.
J Cell Biochem
September 2019
Department of Radiation Oncology, First Hospital of Xi'an Jiaotong Univesity, Xi'an, Shaanxi, China.
Mounting evidence showed that microRNAs involve in development and chemoresistance of various human cancers. We explored the roles and mechanisms of miR-144 in resistance to cisplatin (CDDP) of cervical cancer cells. miR-144 and LIM homeobox 2 (LHX2) expression in CDDP-resistant and the parental cells was determined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis, respectively.
View Article and Find Full Text PDFQuantitative proteomic and interaction network analysis of cisplatin resistance in HeLa cells.
PLoS One
September 2011
Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America.
Cisplatin along with other platinum based drugs are some of the most widely used chemotherapeutic agents. However drug resistance is a major problem for the successful chemotherapeutic treatment of cancer. Current evidence suggests that drug resistance is a multifactorial problem due to changes in the expression levels and activity of a wide number of proteins.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!