p53-independent response to cisplatin and oxaliplatin in MMTV-ras mouse salivary tumors.
A transgenic mouse tumor model was used to investigate the role of p53 in tumor response to two different platinum-based chemotherapeutic agents: (a) cisplatin and (b) oxaliplatin, a diaminocyclohexane platine recently introduced into the clinic. MMTV-v-Ha-ras transgenic mice were interbred to p53-deficient mice to generate mice that develop salivary tumors either possessing or lacking p53. Tumor-bearing mice were then treated on either a 9-day schedule to assess overall tumor growth response or on a short-term treatment schedule to assess effects on cell cycle parameters and apoptosis. Both agents induced significant apoptosis and promoted overall tumor regression, regardless of the p53 status of the tumor. This is in contrast to previous studies using this model in which treatment with paclitaxel or doxorubicin promoted tumor growth arrest but not apoptosis. These findings indicate that even in the context of an activated ras gene that potentially mediates suppression of apoptosis, both cisplatin and oxaliplatin are capable of promoting an efficient p53-independent tumor response.
Petit
Thierry
T
Cancer Therapy and Research Center, The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, USA.
Bearss
David J
DJ
Troyer
Dean A
DA
Munoz
Ruben M
RM
Windle
Jolene J
JJ
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D002945:Cisplatin / Q000627:therapeutic use*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D008297:Male; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009944:Organoplatinum Compounds / Q000627:therapeutic use*; D000077150:Oxaliplatin; D012468:Salivary Gland Neoplasms / Q000188:drug therapy* / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D016159:Tumor Suppressor Protein p53; D000077150:Oxaliplatin; D002945:Cisplatin