Naslov
SMS 201-995 enhances the S-phase block induced by 5-fluorouracil in human colorectal cancer line

Autori
Massari, Dražen ; Trobonjača, Zlatko ; Rukavina, Daniel ; Radošević-Stašić, Biserka

Izvornik
Anti-cancer drugs (0959-4973) 16 (2005), 9; 989-996

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Human colorectal cell line WiDr; SMS 201-995 (Octreotide); cell cycle kinetics; HLA class I expression.

Sažetak
The action of somatostatin analogue SMS-201.995 (SMS) was tested in monotherapy and in combined therapy with cytotoxic agent 5-fluorouracil (5-FU) on cell cycle kinetics of human colon cancer cell line WiDr, expressing a mutant p53 (mp53). The data, obtained by flow cytometric DNA analysis, showed that SMS in dose of 0.2 mg/ml increased the apoptosis, augmenting the proportion of cells with subdiploid DNA content for 65% and 48%, after 3h and 6h, respectively (p<0.01). In cultures lasting 24h and 36h it decreased also the percentages of cells in G0/G1 phase for 22.9% and 14, 3% (p<0.0001), while in dose of 0.1 mg/ml, SMS decreased the percentage of cells in G2/M for 14, 3% (p<0.003). In contrast to SMS, 5-FU (0.1 mg/ml) augmented the apoptosis at 12h (p<0.01), and markedly increased the fraction of cells in S phase, increasing its values from 24-72h for 108%-234% respectively, in comparison with the control. The most evident finding after the combination of SMS (0.2 mg/ml) and 5-FU (0.1 mg/ml) was a potentiation of 5-FU-induced S phase block for further 7, 9%, 12, 9% and 42, 1%, at 24h, 36h and 72h, respectively (p<0.01 and p< 0.001). Treatment with 5-FU upregulated also the HLA class I expression on cancer cells. In this sense, SMS was less effective, and given in combination with 5-FU did not change the effects induced by 5-FU. The data emphasize that SMS has the pro-apoptotic and anti-proliferative effects, which in proper dose combinations might enhance the effects of 5-FU on human colorectal cancer, expressing mp53.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti, Kliničke medicinske znanosti

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