Rapamycin and PF4 Induce Apoptosis by Upregulating Bax and Down-Regulating Survivin in MNU-Induced Breast Cancer

Al-Astani Tengku Din, Tengku Ahmad Damitri; Shamsuddin, Shazana Hilda; Idris, Fauziah Mohamad; Wan Mansor, Wan Nor Ariffin; Abdul Jalal, Muhammad Irfan; Jaafar, Hasnan

추천

검색

자료유형: 학술저널

저자정보: Al-Astani Tengku Din, Tengku Ahmad Damitri (Department of Pathology, School of Medical Sciences, Universiti Sains Malaysia) Shamsuddin, Shazana Hilda (Department of Pathology, School of Medical Sciences, Universiti Sains Malaysia) Idris, Fauziah Mohamad (Department of Microbiology, Universiti Sains Malaysia) Wan Mansor, Wan Nor Ariffin (Biostatistic Unit, School of Medical Sciences, Universiti Sains Malaysia) Abdul Jalal, Muhammad Irfan (Institute for Research in Molecular Medicine [INFORMM], Health Campus, Universiti Sains Malaysia) Jaafar, Hasnan (Department of Pathology, School of Medical Sciences, Universiti Sains Malaysia)

저널정보: 아시아태평양암예방학회 Asian Pacific journal of cancer prevention : APJCP Asian Pacific journal of cancer prevention : APJCP 제15권 제9호

발행연도: 2014.1

수록면: 3,939 - 3,944 (6page)

이용수

📌

연구주제

📖

연구배경

🔬

연구방법

🏆

연구결과

초록· 키워드

오류제보하기

Background: To elucidate the role of rapamycin and PF4 on apoptosis regulation via Bax (pro-apoptosis), Bcl-2 (anti-apoptosis) and survivin activation on the growth in the 1-methyl-1-nitrosourea-induced invasive breast carcinoma model. Materials and Methods: Thirty five female Sprague Dawley rats at age 21-day old were divided into 4 groups; Group 1 (control, n=10), Group 2 (PF4, n=5), Group 3 (rapamycin, n=10) and Group 4 (rapamycin+PF4, n=10). MNU was administered intraperitionally, dosed at 70mg/kg body weight. The rats were treated when the tumors reached the size of $14.5{\pm}0.5mm$ and subsequently sacrificed after 5 days. Rapamycin and PF4 were administered as focal intralesional injections at the dose of $20{\mu}g$/lesion. The tumor tissue was then subjected to histopathological examinations for morphological appraisal and immunohistochemical assessment of the pro-apoptotic marker, Bax and anti-apoptotic markers, Bcl-2 and survivin. Results: The histopathological pattern of the untreated control cohort showed that the severity of the malignancy augments with mammary tumor growth. Tumors developing in untreated groups were more aggressive whilst those in treated groups demonstrated a transformation to a less aggressive subtype. Combined treatment resulted in a significant reduction of tumor size without phenotypic changes. Bax, the pro-apoptotic marker, was significantly expressed at higher levels in the rapamycin-treated and rapamycin+PF4-treated groups compared to controls (p<0.05). Consequently, survivin was also significantly downregulated in the rapamycin-treated and rapamycin+PF4-treated group and this was significantly different when compared to controls (p). Conclusions: In our rat model, it could be clearly shown that rapamycin specifically affects Bax and survivin signaling pathways in activation of apoptosis. We conclude that rapamycin plays a critical role in the induction of apoptosis in MNU-induced mammary carcinoma.

#Breast cancer #apoptosis #Bax #Bcl-2 #survivin #rapamycin

참고문헌 (0)

참고문헌 신청

참고문헌이 DBpia에서 서비스 중이라면, [참고문헌 신청]을 통해 등록해보세요