Anti-MDR tumor mechanism of CIP-36, a podophyllotoxin derivative.
- Author:
Xin MEI
1
;
Yun-gen JIANG
;
Jing-jing LÜ
;
Ke-zhu WU
;
Bo CAO
;
Hong CHEN
Author Information
1. Department of Pharmacognosy, Medical College of Chinese People's Armed Police Forces, Tianjin 300162, China.
- Publication Type:Journal Article
- MeSH:
ATP Binding Cassette Transporter, Sub-Family B;
ATP-Binding Cassette, Sub-Family B, Member 1;
genetics;
metabolism;
Antineoplastic Agents, Phytogenic;
administration & dosage;
pharmacology;
Apoptosis;
drug effects;
Carcinoma, Squamous Cell;
metabolism;
pathology;
Caspase 3;
genetics;
metabolism;
Cell Line, Tumor;
Cell Proliferation;
drug effects;
Dose-Response Relationship, Drug;
Drug Resistance, Multiple;
Drug Resistance, Neoplasm;
Humans;
KB Cells;
Mouth Neoplasms;
metabolism;
pathology;
Podophyllotoxin;
administration & dosage;
analogs & derivatives;
pharmacology;
Proto-Oncogene Proteins c-bcl-2;
genetics;
metabolism;
Proto-Oncogene Proteins p21(ras);
genetics;
metabolism;
RNA, Messenger;
metabolism;
Tumor Suppressor Protein p53;
genetics;
metabolism;
bcl-2-Associated X Protein;
genetics;
metabolism
- From:
Acta Pharmaceutica Sinica
2011;46(10):1193-1198
- CountryChina
- Language:Chinese
-
Abstract:
This study is to investigate the antitumor activity of CIP-36 on multidrug resistant human oral squamous carcinoma cell line (KBV200 cells) in vitro and the possible anticancer mechanisms. MTT assay, Hoechst fluorescein stain, RT-PCR and immunohistochemistry were carried out on KBV200 and KB cells. The growth of many tumor cells was obviously inhibited by CIP-36, especially the multidrug resistant cells KBV200. Obvious apoptosis could be observed in the Hoechst 33342 staining experiments. The results of RT-PCR showed that the levels of p53, p21, caspase-3 and bax mRNA increased, and meanwhile the expression of mdr-1 and bcl-2 mRNA decreased in a dose-dependent manner. The data were significantly different from that of vehicle. The expression of P-gp significantly decreased with the increasing dosage of CIP-36 examined by immunohistochemistry. It can be concluded that CIP-36 could change resistance-related genes and proteins to overcome multidrug resistance in the KBV200 cell line.
