Apoptosis in human hepatoma cell lines by chemotherapeutic drugs via Fas-dependent and Fas-independent pathways

Many chemotherapeutic drugs have been found to exert their mode of action v ia induction of apoptosis in cancer cells. The mechanisms involved in this process are not clear. Recent studies have shown that the Fas/Fas ligand (F asL) system is a key factor controlling apoptotic cell death. In the presen t study, the involvement of Fas in chemotherapeutic drug-induced apoptosis in hepatoma cell lines was investigated. Five different human hepatoma cell lines, Hep G2, Rep G2.2.15, Hep 3B, SK-Hep-1, and PLC/PRF/5, were used. It was found that they expressed different levels of Fas. However, all five c ell lines were susceptible to apoptosis when treated with chemotherapeutic drugs such as 5-fluorouracil (5-FU) or cisplatin. In Rep G2 that constituti vely expressed Fas, 5-FU or cisplatin treatment caused an increase in the e xpression of Fas before the formation of oligonucleosomal DNA fragments, a typical feature of apoptosis. However, in Hep 3B, where Fas is undetectable , apoptosis could also be induced by 5-FU or cisplatin without induction of Fas. The agonistic anti-Fas antibody (CH-11) was capable of inducing apopt osis by itself and promoted drug-induced apoptosis in Rep G2 but not in Hep 3B, The antagonistic anti-Fas antibody (ZB4) inhibited drug-induced apopto sis in Hep G2, Our results suggest that apoptosis can be induced in hepatom a cell Lines via both Fas-dependent and Fas-independent pathways.