Relationships Between Induction Of Apoptosis By Taxol And CDDP In MCF-7/ADR And Hela Cells And Apoptosis-related Proteins And Ca～(2+)

Apoptosis is a process of cell death that actively carries out the suicide process under the control of a series of gene regulators.The occurance and development of tumor are the result of the ability of loss in apoptosis of tumor cells.Thus, the effectiveness of anticancer drugs may not simply reflect their ability to cause cellular damage, but also the cell's ability to detect and respond to this damage. However, until recently, the tumor-specific toxicity of most anticancer agents was attributed to their debilitating effects on actively proliferating cells. Most recently, it has become apparent that most anticancer agents induce apoptosis. Current evidences suggest that apoptosis is controlled by genes such as bcl-2, bax, Pcna, HSP7O, NF-KB and caspase-3 et al . Pro- and anti-apoptosis of these proteins were controversial. Metal ions such as Ca2+ Cu2+,Mg+,Zn2~ take part in the different functions such as signal transduction, apoptosis, regulation of enzymes activities etc. Especially the relationship between apoptosis and Ca2~ had been focused on. Increased in intracellular Ca2~ concentration have been shown to trigger apoptosis and numerous apoptosis inducers increase [Ca2+]i. 6 Together taken, in this study, we examined the expression levels of apoptosis-related proteins bcl-2, bax, PCNA, HSP7O, NF-kB and to determine the relationship between their changes and apoptosis. In addition, we investigated the changes of Ca2+ during the effects of CDDP, Taxol and a-TNF on Hela cell. 1. Effects of taxol, CDDP, Heat and a-TNF on apoptosis in MCF-7/ADR and Hela cells. To investigate the effects of taxol and CDDP as well as in combination with heat and a-TNF on apoptosis in MCF-7/ADR and Hela cells. The apoptotic cells were detected by TU7NEL, HE, eletronic micrpscopy and flow cytometty method .The results followed as: HeLa cells exposed to CDDP and Taxol undergo cell death, presenting morphological and biochemical characteristics typical of apoptosis and the apoptotic cells increased with time and concentration. CDDP may give rise to the death of MCF-7/ADR, but did not cause the apoptosis of MCF-7/ADR. Treatment of MCF-7/ADR cell with taxol resulted in characteristics typical of apoptosis. a-TNF induced apoptosis of MCF-7/ADR and Hela cells with time and concentration increase in apoptotic cell index. Hela cell was more susceptible to a-TNF than MCF-7/ADR. The synergistic effect of CDDP in combination with a-TNF and heat were observed. CDDP (1.5mg·L-1 in combination with heat(400C or 440C) had synergistic effect on HeIa, but (0.1-0.5mg·L-1 in combination with heat(40-420C) had antagonistic effect on Hela. Cells with multiple micronuclei were observed in Hela and MCF-7/ADR cells treated with Taxol, but not with CDDP, a-TNF and heat (20mm). Taken together, All of Taxol, CDDP, a-TN7F and heat may induced apoptosis in Hela cell. Taxol in combination with a-TNF and CDDP in combination with heat had no synergistic effect on MCF-7/ADR or Hela cell. Low concentration of CDDP in combination with moderate hyperthermia had antagonistic effect on Hela. The 7 mechanism are to be fuether studied. 2. The relationship between apoptosis induced by Taxol and CDDP as well as in combination wi...