Influence of antitumor drugs on the expression of Fas system in SW480 colon cancer cells.
OBJECTIVE
To observe the influence of popular antitumor drugs [5-fluorouracil (5-FU), mitomycin (MMC), cisplatin (CP) and all-trans retinoic acid (ATRA)] on the expression of Fas system in SW480 colon cancer cells.


METHODS
The expressions of Fas/FasL protein and mRNA in colon cancer line SW480 cells before and after the treatment of the antitumor drugs (5-FU, MMC, CP and ATRA) were detected by immunocytochemistry, flow cytometry and reverse-transcriptase polymerase chain reaction. Coculture assays of colon cancer cells and Jurkat cells (Fas-sensitive cells) were performed to observe the counterattack of colon cancer cells to lymphocytes. Apoptosis of Jurkat cells were detected by flow cytometry and fluorescence microscopy.


RESULTS
SW480 expressed high FasL and low Fas without drug treatments. When treated with 5-FU, Fas expression rates in SW480 increased, but FasL remained unchanged. Both Fas and FasL increased significantly when treated with MMC and CP. Most importantly, ATRA could induce SW480 cells to differentiate, increase the expression of Fas and decrease the expression of FasL. The coculture of SW480 cells and Jurkat cells confirmed the function of FasL in the SW480 cells.


CONCLUSIONS
Certain antitumor drugs can change the expression of the Fas system in SW480 cells in different ways. In vitro, MMC and CP can increase the sensitivity of colon cancer cells to apoptosis signals, but they possibly facilitate immune escape of tumor cells. 5-FU results in immune escape of colon cancer cells. ATRA can down-regulate the possibility of counterattack of colon cancer cells.
Zhu
Qiang
Q
Department of Gastroenterology, Shandong Provincial Hospital, Shandong, Province, China. zhuqiang@medmail.com.cn
Liu
Ji-yong
JY
Yang
Chong-mei
CM
Xu
Hong-wei
HW
Zhang
An-zhong
AZ
Cui
Yi
Y
Wang
Hong-bo
HB
Qin
Cheng-yong
CY
Li
Yan-qing
YQ
D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D018920:Coculture Techniques; D003110:Colonic Neoplasms / Q000276:immunology* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism; D005472:Fluorouracil / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D019169:Jurkat Cells; D016685:Mitomycin / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism*
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D053222:Fas Ligand Protein; D012333:RNA, Messenger; D019014:fas Receptor; D016685:Mitomycin; D014212:Tretinoin; D002945:Cisplatin; D005472:Fluorouracil