Department of Surgery, Chi-Mei Medical Center, Tainan, Taiwan.
Department of Sports Management, College of Leisure and Recreation Management, Chia Nan University of Pharmacy and Science, Tainan, Taiwan.
J Cell Physiol. 2018 Jun;233(6):4618-4625. doi: 10.1002/jcp.26156. Epub 2018 Jan 15.
Simvastatin (SIM), a widely used cholesterol-lowering drug, also exhibits tumor-suppressive potentials in several types of malignancy. Colorectal cancer (CRC), the third most common malignant neoplasm, accounts for the second most leading cause of cancer-related deaths worldwide. In the present study, we investigated the anticancer effects of SIM on CRC using primary cancer cells lines (CPs: CP1 to CP5) isolated from five Taiwanese colorectal cancer patients as a model for colorectal cancer. We treated all five CPs with SIM for 24-72 hr and observed the respective cell viability by an MTT assay. SIM increased DNA content of the G phase, but did not induce apoptosis/necrosis in CPs as shown by flow cytometry with propidium iodide (PI)/annexin V double staining and PI staining. The expression of G phase-related proteins was analyzed by RT-PCR and Western blotting. SIM suppressed cell growth and induced cell cycle G -arrest by suppressing the expression of CDK4/cyclin D1 and CDK2/cyclin E1, but elevating the expression of glycogen synthase kinase 3β in CPs. Our findings indicate that SIM may have antitumor activity in established colorectal cancer.
辛伐他汀（SIM）是一种广泛应用于降低胆固醇的药物，它在几种恶性肿瘤中也表现出肿瘤抑制作用。结直肠癌（CRC）是第三大常见恶性肿瘤，是全球癌症相关死亡的第二大主要原因。在本研究中，我们使用从 5 名台湾结直肠癌患者中分离出的原代癌细胞系（CPs：CP1 至 CP5）作为结直肠癌模型，研究了 SIM 对 CRC 的抗癌作用。我们用 SIM 处理所有 5 个 CPs24-72 小时，并通过用碘化丙啶（PI）/膜联蛋白 V 双重染色和 PI 染色的流式细胞术观察各自的细胞活力。通过 RT-PCR 和 Western blot 分析 G 期相关蛋白的表达。SIM 通过抑制 CDK4/细胞周期蛋白 D1 和 CDK2/细胞周期蛋白 E1 的表达，同时升高糖原合酶激酶 3β的表达，抑制细胞生长并诱导细胞周期 G 期阻滞。我们的研究结果表明，SIM 可能对已建立的结直肠癌具有抗肿瘤活性。
