Increased expression of p27 is associated with the cisplatin resistance in gastric cancer cell line YCC-3.
The major obstacle of treating cancer patients is acquisition of chemoresistance, in which treated tumor cells become insensitive after chronic drug exposure. To study the mechanism of acquired cisplatin resistance, we established a cisplatin-resistant human gastric cancer cell line. The cisplatin-resistant cell line (YCC-3/R) was isolated after exposing the gastric cancer cell line, YCC-3, to a constant concentration (0.5 microg/mL) of cisplatin for 12 months. The expression of cell cycle regulatory proteins (p53, Bax, p21, p27) in the YCC-3/R were investigated by western blot analysis. The cisplatin treatment significantly down-regulated the p53 and p21 expression level, while up-regulated the p27 expression in the YCC-3/R cells compared to the parental cells. The Bax expression level was similar in both cells. These results suggest that the p27 dependent-cell cycle arrest may prevent cisplatin-induced apoptosis and give enough time to repair the DNA damage in the YCC-3/R cells.
Le
Tuong Vy Thi
TV
Sungkyunkwan University, Suwon, Korea.
Seo
Youngcheol
Y
Ryu
Chun Jeih
CJ
Lee
Hye Ran
HR
Park
Hyun-Ju
HJ
D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology* / Q000627:therapeutic use; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
C436291:CDKN1B protein, human; D047908:Intracellular Signaling Peptides and Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D002945:Cisplatin