[The mechanism of topotecan resistance in ovarian cancer cell line].

Abstract

OBJECTIVE:

To study the mechanism of topotecan (TPT) resistance in ovarian cancer cell line.

METHODS:

A TPT-resistant ovarian cancer cell line A2780/TPT established in this laboratory was used in this study. Intracellular rhodamine fluorescence intensity of the TPT-resistant cells and parental cells were measured by flow cytometry. The gene expression of membrane protein transporter such as transporter P-glycoprotein (P-gp), multidrug resistance associated protein (MRP), breast cancer resistance protein (BCRP) was evaluated by RT-PCR. The antisense-phosphorothioate oligonucleotide (ASODN) including a translation initiation site of BCRP mRNA was transferred into resistant cells by liposome.

RESULTS:

Intracellular rhodamine fluorescence intensity of the resistant cells was 31.19% of that in the parental cells (P < 0.01). No expression of P-gp was demonstrated, and that of MRP was very weak in the TPT-resistant cells (relative expression value = 0.057). BCRP was overexpressed in the TPT-resistant cells (relative expression = 0.66), but not in the parental cells. Transfer of ASODN into resistant cells resulted in a 59.42% reduction of BCRP gene expression (P < 0.05) and an obviously increased intracellular rhodamine fluorescence intensity from 5.42 to 16.63 (P < 0.05).

CONCLUSION:

The overexpression of BCRP which mediated drug efflux may play an important role in the induction of TPT-resistance in ovarian cancer.

• Authors: Ping Jia, Shao-Bo Wu, Fang Li, Qian Xu, Ming-Fu Wu, Guo-Ning Liao, Yun-Ping Lu, Ding Ma
• Journal: Zhonghua zhong liu za zhi [Chinese journal of oncology] (Zhonghua Zhong Liu Za Zhi) Vol. 26 Issue 3 Pg. 139-42 (Mar 2004) ISSN: 0253-3766 [Print] China
• PMID: 15196431 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ABCG2 protein, human
• ATP Binding Cassette Transporter, Subfamily B, Member 1
• ATP Binding Cassette Transporter, Subfamily G, Member 2
• ATP-Binding Cassette Transporters
• Antineoplastic Agents
• Neoplasm Proteins
• RNA, Messenger
• Topotecan

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (genetics)
• ATP Binding Cassette Transporter, Subfamily G, Member 2
• ATP-Binding Cassette Transporters (genetics)
• Antineoplastic Agents (pharmacology)
• Cell Line, Tumor
• Drug Resistance, Neoplasm
• Female
• Humans
• Neoplasm Proteins (genetics)
• Ovarian Neoplasms (drug therapy, pathology)
• RNA, Messenger (analysis)
• Topotecan (pharmacology)