Assessment of the Chemosensitivity of Uveal Melanoma Cells Ex Vivo
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Cell Technologies in Biology and Medicine, No. 3, November, 2020
Assessment of the Chemosensitivity of Uveal Melanoma Cells Ex Vivo S. V. Saakyan1,3, А. Yu. Tsygankov1,3, N. I. Moiseeva2, А. F. Karamysheva2, and D. D. Garri3
Translated from Kletochnye Tekhnologii v Biologii i Meditsine, No. 3, pp. 185-190, September, 2020 Original article submitted May 15, 2020 The study was designed to create a primary cell culture of uveal melanoma and to evaluate its resistance to chemotherapy. Of the obtained 20 samples of uveal melanoma, the primary cultures with proliferation sufficient for MTT test were derived in only 7 cases. However, even these cultures were unable to survive more than 4 passages; the cells accumulated melanin and underwent apoptosis. Retinol palmitate and nepafenac produced no cytotoxic effect on uveal melanoma cells. Of 5 cultures treated with sodium valproate (Convulex), no pronounced cytotoxic effect was observed in one culture (UM4); in 2 cultures, 50% cells died in the presence of the lowest drug concentration of 1.88 mg/ml; and in 2 cultures, the same effect was achieved at drug concentrations 7-10 mg/ml. The cytotoxic effect of treosulfan was evaluated in only 4 cultures of uveal melanoma: the drug exhibited pronounced antitumor activity on all cultures, in 2 cases, it was effective at a concentration of 0.16 mg/ml. Gemcitabine in a concentration of 2.5 mg/ml produced a pronounced cytotoxic effect in 4 out of 7 cultures (death of 70-80% cells) and induced death of ~45% cells in the remaining 3 cultures. Mitoxantrone had ambiguous effect: in 2 of 5 cultures, the drug in high concentrations stimulated the growth of tumor cells, but in 3 cultures, the drug even in minimum concentrations induced death of 70-80% cells. Key Words: uveal melanoma; chemotherapy; cell culture; MTT test Uveal melanoma (UM) is the most common primary malignant intraocular tumor in the adult population; it constitutes ~3% of all melanomas [19]. UM originates from melanocytes in the uveal tract, including the iris, ciliary body, and choroid; in most cases (85%), the tumor is located in the choroid. The incidence of UM is 6-8 cases per 1 million population per year and remains stable over the past decades [1,22,23]. The risk factors of UM are light (blue and gray) eye color, light skin color, UV irradiation, dysplastic cutaneous nevi, ocular melanocytosis, and mutations in GNAQ/GNA11 and BAP1 genes [2,3,13,18]. Helmholtz National Medical Research Center of Eye Diseases, Min istry of Health of the Russian Federation, Moscow, Russia; 2 N. N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, Moscow, Russia; 3A. I. Evdokimov Moscow State University of Medicine and Dentistry, Ministry of Health of the Russian Federation, Moscow, Russia. Address for correspondence: [email protected]. A. Yu. Tsygankov 1
Distant metastases develop in about a half of the patients with UM due to hematogenous spreading to the liver (89%), lungs (29%), bones (17%), skin and subcutaneous fat
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