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[Apoptosis and chemosensitivity]
Abstract:
Many antineoplastic drugs and cytotoxic irradiation induce apoptosis in cancer cells. ICE and ICE-like proteases play important roles in drug-induced apoptosis of cancer cells. We evaluated the cellular factors affecting susceptibility to apoptosis using gene-transfected cells. Introduction of bcl 2 gene into human small cell lung cancer cells conferred resistance to mitomycin C and irinotecan. DNA fragmentation was reduced in these cells. These results indicate apoptosis is one of the mechanisms of cell death caused by some antineoplastic drugs. Investigations are ongoing to elucidate the contribution of the Bcl 2 family proteins to antineoplastic drug induced apoptosis. Wild type p53-transfected cancer cells were sensitive to anticancer drugs. On the other hand, p53-depleted cells were reported to be more sensitive to taxanes than p53-proficient cells. Introduction of Rb gene and p16-gene enhanced cytotoxicity of taxanes and topoisomerase I inhibitors, respectively. In clinical studies, patients of non small cell lung cancer with high expression of Bcl-2 were reported to show longer survival than patients with lower expression. However, this result may be confusing because Bcl-2 reduced the efficacy of antineoplastic drugs. Further evaluation is required to determine the cellular proteins serving as markers for treatment efficacy or prognosis.
Insights
Cellular factors like Bcl-2 influence cancer cell death from chemotherapy. Understanding these apoptosis mechanisms can guide treatment efficacy and prognosis for cancer patients.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Antineoplastic drugs and irradiation induce apoptosis (programmed cell death) in cancer cells.
- ICE and ICE-like proteases are crucial in drug-induced apoptosis.
- Cellular factors significantly impact cancer cell susceptibility to apoptosis.
Purpose of the Study:
- To evaluate cellular factors influencing apoptosis in cancer cells.
- To investigate the role of gene transfection in modulating cancer cell response to anticancer drugs.
Main Methods:
- Gene transfection of human small cell lung cancer cells with bcl 2, p53, Rb, and p16 genes.
- Assessment of cellular resistance and DNA fragmentation following drug treatment (mitomycin C, irinotecan, taxanes, topoisomerase I inhibitors).
Main Results:
- Introduction of the bcl 2 gene conferred resistance to mitomycin C and irinotecan, reducing DNA fragmentation.
- Wild-type p53-transfected cells showed sensitivity to anticancer drugs.
- p53-depleted cells were more sensitive to taxanes.
- Rb and p16 gene introduction enhanced cytotoxicity of specific anticancer agents.
Conclusions:
- Apoptosis is a key mechanism of cell death induced by certain antineoplastic drugs.
- Bcl 2 family proteins play a role in drug-induced apoptosis, but their clinical prognostic value requires further investigation.
- Cellular proteins like p53, Rb, and p16 influence cancer cell sensitivity to various chemotherapeutic agents.