Abstract B27: Assessment of chemotherapeutic responses to neoadjuvant FOLFOX and Aspirin on BIRC7 in colorectal adenocarcinoma cells induced in Albino rats

Abstract

Abstract Chemotherapeutic resistance is a problem in the management of malignant tumors especially colorectal adenocarcinoma. Overexpression of Baculoviral IAP repeat-containing protein-7 (BIRC7) was previously reported by this study group to limit the cytotoxic efficacy of neoadjuvant folinic acid, 5-fluorouracil and oxaliplatin (FOLFOX) chemotherapy regimen on human colorectal cancer cells in-vivo. And a significant inhibitory effect of Aspirin on the BIRC7 protein in p53 mutant SW480 colon cancer cells in-vitro was also found. Our aim now is to access the efficacy of the addition of Aspirin to neoadjuvant FOLFOX-chemotherapy on colorectal cancer cells in-vivo using the N-methyl-N-nitrosourea (NMU) carcinogen-induced model on albino rats per rectum. A total of 180 male Albino rats whose weight falls between 110-150g will be used. They will be grouped into 18 sets of 10 rats each and a three staged study will be performed. Namely, assessment of health parameters before the cancer induction, assessments on confirmation of cancer induction and assessments after chemotherapeutic intervention. The chemotherapeutic intervention will be further subdivided into mono, bi or tri therapy in various combinations with and without the addition of the Aspirin. The addition of Aspirin to the chemotherapy regimen will be further divided into concurrent and sequential addition. NMU will be administered at a dose of 2 mg/kg intra rectally every other day until the development of colorectal cancer which, will be confirmed by barium enema and histological analysis. Aspirin will be administered at a dose of 25 mg/kg or 12.5 mg/kg. Folinic acid will be administered at a dose of 7 mg/kg or 3.5 mg/kg intraperitoneally (i.p). Oxaliplatin will be dministered at a dose of 3 mg/kg or 1.5 mg/kg i.p. And 5-FU will be administered at a dose of 50 mg/kg or 25 mg/kg i.p. The animals' hemogram and other pertinent investigations will be done ultimately including culling for histological assessment of tumors. The tumors will be processed for H&E histological analysis, immunohistochemistry, immunofluorescence, ELISA and immunoblot using Anti-BIRC7, COX-2, NFK-B, P53, Annexin, MSH2, MSH6, PMS2, and MLH1 antibodies. Findings show that at full sequential dose of Aspirin with chemotherapy there was absence of both significant BIRC7 expression and histologically residual detectable tumor in the colon of the Albino rats. Furthermore, results from the concurrent treatment of Aspirin and FOLFOX in full dose compound to half dose of both sequential and concurrent show that there was significant tumor regression when compared with the untreated colon tumor bearing Albino Rats. The study also shows a survival advantage of the group of Albino rats treated sequentially compared other groups. The study showed that Aspirin given at full therapeutic dose prior to neoadjuvant chemotherapy makes the tumor cells highly chemosensitive and may have a role in the finding of having no detectable cancer cells in the colon and also reduced BIRC7 expression. By implication, Aspirin primes the colorectal cancer cells for neoadjuvant chemotherapeutic efficacy and this may be important for management of colorectal cancer patients. Citation Format: Mohammed Faruk, Sani Ibrahim, Surajo Mohammed Aminu, Adamu Abdullahi, Ahmed Adamu, Yawale Iliyasu, Mohammed Shehu Shehu, John Idoko, Abdullahi Jibril Randawa, Atara Ntekim, Saad Aliyu Ahmed, Abubakar Sani, Khalid Zahir Shah, Yahaya Ukwenya, Cheh Augustine Awasum, Kasimu Umar Adoke, Andrew Jonathan Nok. Assessment of chemotherapeutic responses to neoadjuvant FOLFOX and Aspirin on BIRC7 in colorectal adenocarcinoma cells induced in Albino rats. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Targeting the Vulnerabilities of Cancer; May 16-19, 2016; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(1_Suppl):Abstract nr B27.