Abstract：
Canine oral melanoma is a highly malignant cancer with a poor prognosis. Statins, commonly used drugs for treating dyslipidemia, exhibit pleiotropic anticancer effects and marked anti-proliferative effects against melanoma cells. The anticancer effects among statins vary; in human cancers, lipophilic statins have shown stronger anticancer effects compared with hydrophilic statins. However, data on the differences in the effects of various statins on canine cancer cells are lacking, hence the optimal statins for treating canine melanoma remain unknown. Therefore, this study aimed to clarify the most effective statin by comparing the anticancer effects of hydrophilic rosuvastatin and lipophilic atorvastatin, simvastatin, fluvastatin and pitavastatin on three canine oral melanoma cell lines. Time-dependent measurement of cell confluence showed that lipophilic statins had a stronger anti-proliferative effect on all cell lines than hydrophilic rosuvastatin. Quantification of lactate dehydrogenase release, an indicator of cytotoxicity, showed that lipophilic statins more effectively induced cell death than hydrophilic rosuvastatin. Lipophilic statins affected both inhibition of cell proliferation and induction of cell death. The anticancer effects of statins on canine oral melanoma cells differed in the following ascending order of IC50 values: pitavastatin < fluvastatin = simvastatin < atorvastatin < rosuvastatin. The required concentration of pitavastatin was approximately 1/20th that of rosuvastatin. Among the statins used in this study, pitavastatin had the highest anticancer effect. Our results suggest lipophilic pitavastatin as the optimal statin for treating canine oral melanoma.
摘要：
犬口腔黑色素瘤是一种高度恶性的癌症，预后不良。他汀类药物,常用的治疗血脂异常的药物，对黑素瘤细胞具有多效抗癌作用和明显的抗增殖作用。他汀类药物的抗癌作用各不相同；在人类癌症中，与亲水性他汀相比，亲脂性他汀类药物显示出更强的抗癌作用。然而,缺乏各种他汀类药物对犬癌细胞影响差异的数据，因此，治疗犬黑色素瘤的最佳他汀类药物仍然未知。因此,这项研究旨在通过比较亲水性瑞舒伐他汀和亲脂性阿托伐他汀的抗癌作用来阐明最有效的他汀类药物，辛伐他汀,氟伐他汀和匹伐他汀对三种犬口腔黑色素瘤细胞系的影响。细胞融合的时间依赖性测量表明，亲脂性他汀类药物对所有细胞系的抗增殖作用均强于亲水性瑞舒伐他汀。乳酸脱氢酶释放的定量，细胞毒性的指标，结果表明，亲脂性他汀类药物比亲水性瑞舒伐他汀更有效地诱导细胞死亡。亲脂性他汀类药物影响细胞增殖的抑制和细胞死亡的诱导。他汀类药物对犬口腔黑素瘤细胞的抗癌作用在以下IC50值的升序上不同:匹伐他汀<氟伐他汀=辛伐他汀<阿托伐他汀<瑞舒伐他汀。匹伐他汀的所需浓度约为瑞舒伐他汀的1/20。在这项研究中使用的他汀类药物中，匹伐他汀的抗癌作用最高。我们的结果表明，亲脂性匹伐他汀是治疗犬口服黑色素瘤的最佳他汀类药物。
