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Journal of the Korean Society of Coloproctology 2005;21(3):129-137.
Expression and Function of ABC Transporters as Multidrug Resistance Mechansims in Colon Cancer Cells.
Jeong, Gui Ae , Kim, Kyung Jong , Min, Young Don , Lee, Tae Bum , Kang, Sung In , Jung, Kwon Ryul , Choi, Cheol Hee
1Department of Surgery, Chosun University Medical School, Gwangju, Korea. kjkim@chosun.ac.kr
2Research Center for Resistant Cells, Chosun University Medical School, Gwangju, Korea.
3Department of Pharmacology, Chosun University Medical School, Gwangju, Korea.
Abstract
PURPOSE
Multidrug resistance (MDR) is a phenomenon whereby tumor cells acquire resistance to a broad range of structurally and functionally diverse chemotherapeutic drugs. The most widely implicated mechanism of MDR is that concerned with altered membrane transporters in tumor cells. P-glycoprotein (Pgp), multidrug resistance protein (MRP), and breast-cancer-resistance protein (BCRP) are well-known membrane transporters that pump out antitumor agents by using an ATP-dependent process, the so-called ATP-binding cassette (ABC) superfamily or transporter. This study was undertaken to test the prevalence of each ABC transporter and to determine which transporter has functional acitivity in various colon cancer cells.
METHODS
Expressions of Pgp, MRP, and BCRP mRNA were determined in 9 colon-cancer cell lines by using an RT-PCR assay. The sensitivity to anticancer agents substrate for each ABC transporter in the colon cancer cells determined using an MTT assay. The accumulation of fluorescent compounds for functional detection of each ABC transporter was determined by using flow cytometry.
RESULTS
Pgp mRNA was variably expressed in 6 of 9 colon cancer cells lines. MRP and BCRP mRNA were expressed in all the 9 cell lines. A smaller cytotoxic effect to paclitaxel and a smaller amount of rhodamine123 accumulation were observed in Colo 320HSR expressing the highest levels of Pgp than in SNU-C5 not expressing Pgp. These effects in Colo320HSR were reversed with the addition of various Pgp inhibitors, but such a reversal did not occur in SNU-C5. The cytotoxic effect to VP-16 was not related to the expression levels of MRP in Colo320HSR and SNU-C, but the amount of calcein-AM accumulation was reversed with addition of probenecid, MRP inhibitor. The cytotoxic effect and the drug accumulation of mitoxantrone were not related to the expression levels of BCRP.
CONCLUSIONS
This study suggests that of the ABC transporters, primarily Pgp and MRP have functional activity in colon cancer cell lines.
Key Words: Colon cancer; Multidrug resistance (MDR); ABC transporter


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