Abstract
Effect of irradiation alone and irradiation after 5-fluorouracil (5-FU), paclitaxel, or cisplatin (CDDP) was investigated in human cervical cell lines (CaSki, ME180, SiHa, and C33A). High-risk human papillomavirus (HPV) (+) CaSki and SiHa cells were the most resistant to CDDP, 5-FU, and radiation treatments. Radiation and CDDP and 5-FU resulted in decreased survival of HPV 16 and 18 (+) cells, whereas addition of paclitaxel to radiation treatments decreased killing. Enhanced killing of ME180 cells containing HPV39 sequences was demonstrated with chemoradiotherapy with all agents. HPV(-) C33A was more sensitive to radiation than the other cell lines, and the addition of chemotherapeutic agents did not result in significant change in cytotoxicity. Expression of survivin was inversely proportional to cell sensitivity to CDDP, 5-FU, and radiation. Constitutive AKT levels are the lowest in cell lines that are the most resistant to CDDP, 5-FU, and radiation. These data provide correlation of response to combined therapeutic modalities with HPV status of cervical cancer and expression of survivin and AKT.
MeSH terms
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Antimetabolites, Antineoplastic / pharmacology
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Antineoplastic Agents / pharmacology
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Antineoplastic Agents / therapeutic use*
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Antineoplastic Agents, Phytogenic / pharmacology
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Cell Line, Tumor / drug effects
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Cell Line, Tumor / radiation effects
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Cell Survival / drug effects
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Cell Survival / radiation effects
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Drug Resistance, Neoplasm
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Female
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Fluorouracil / pharmacology
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Humans
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Inhibitor of Apoptosis Proteins
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Microtubule-Associated Proteins / metabolism
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Neoplasm Proteins
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Paclitaxel / pharmacology
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Papillomaviridae*
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Papillomavirus Infections / complications*
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Protein Serine-Threonine Kinases / metabolism
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-akt
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Survivin
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Uterine Cervical Neoplasms / drug therapy*
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Uterine Cervical Neoplasms / physiopathology
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Uterine Cervical Neoplasms / radiotherapy*
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Uterine Cervical Neoplasms / virology
Substances
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Antimetabolites, Antineoplastic
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Antineoplastic Agents
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Antineoplastic Agents, Phytogenic
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BIRC5 protein, human
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Inhibitor of Apoptosis Proteins
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Microtubule-Associated Proteins
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Neoplasm Proteins
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Proto-Oncogene Proteins
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Survivin
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AKT1 protein, human
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
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Paclitaxel
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Fluorouracil