Department of Pathology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Malaysia.
Department of Chemical Pathology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Malaysia.
Asian Pac J Cancer Prev. 2020 Oct 1;21(10):2919-2925. doi: 10.31557/APJCP.2020.21.10.2919.
To analyze the effect of sirolimus and sunitinib in blocking the tumor growth and to evaluate the expressions of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor-2 (HER2/neu) after treated with sirolimus and sunitinib.
Thirty-two female Sprague Dawley rats at age 21-days old were administered intraperitoneally with N-Methyl-N-Nitroso Urea (NMU), dosed at 70mg/kg body weight. The rats were divided into 4 groups; Group 1 (Control, n=8), Group 2 (Sirolimus, n=8), Group 3 (Sunitinib, n=8) and Group 4 (Sirolimus+Sunitinib, n=8), being treated twice when the tumor reached the size of 14.5±0.5 mm and subsequently sacrificed after 5 days. The protein expressions of ER, PgR and HER2/neu of the tumor tissues were evaluated by using immunohistochemistry analysis.
Treatment with sirolimus alone lowered expressions of ER and PgR of breast cancer and reduced tumor size. There was no significant difference of ER and PgR expressions between control and sunitinib treated tumor. Sunitinib treated tumors reduce in diameter after the first treatment, however the diameter increases after the second treatment. Histologically, sunitinib treated tumor did not show any aggressive invasive carcinoma of no special type (NST) histological subtypes. In addition, all NMU-induced tumors are HER2/neu-negative scoring.
Sirolimus is neither synergistic nor additive with sunitinib for breast cancer treatment.
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分析西罗莫司和舒尼替尼阻断肿瘤生长的效果，并评估西罗莫司和舒尼替尼治疗后雌激素受体（ER）、孕激素受体（PgR）和人表皮生长因子受体-2（HER2/neu）的表达。
方法：32 只 21 天大的 Sprague Dawley 雌性大鼠经腹腔注射 N-甲基-N-亚硝基脲（NMU），剂量为 70mg/kg 体重。大鼠分为 4 组；第 1 组（对照组，n=8）、第 2 组（西罗莫司组，n=8）、第 3 组（舒尼替尼组，n=8）和第 4 组（西罗莫司+舒尼替尼组，n=8），当肿瘤大小达到 14.5±0.5mm 时，每组大鼠进行两次治疗，然后在 5 天后处死。采用免疫组织化学分析评估肿瘤组织中 ER、PgR 和 HER2/neu 的蛋白表达。
结果：西罗莫司单独治疗可降低乳腺癌 ER 和 PgR 的表达并缩小肿瘤体积。对照组和舒尼替尼治疗组肿瘤的 ER 和 PgR 表达无显著差异。舒尼替尼治疗的肿瘤在第一次治疗后直径减小，但第二次治疗后直径增加。组织学上，舒尼替尼治疗的肿瘤没有任何侵袭性非特殊型（NST）组织学亚型的侵袭性。此外，所有 NMU 诱导的肿瘤均为 HER2/neu 阴性评分。
结论：西罗莫司与舒尼替尼联合用于乳腺癌治疗既非协同作用也非相加作用。
