Mn-SOD antisense upregulates in vivo apoptosis of squamous cell carcinoma cells by anticancer drugs and γ-rays regulating expression of the BCL-2 family proteins, COX-2 and p21

✍ Scribed by Eisaku Ueta; Kazunori Yoneda; Tsuyoshi Kimura; Yukihiro Tatemoto; Sayoko Doi; Tetsuya Yamamoto; Tokio Osaki

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: French
• Weight: 388 KB
• Volume: 94
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.1513

✦ Synopsis

ROIs and their scavengers are associated with apoptosis induction by anticancer drugs and ␥-rays, but the details have not been clarified. We examined the effect of transfection of Mn-SOD antisense on apoptosis by 5-FU, PLM, CDDP and ␥-rays using nu/nu mice. After inoculation of Mn-SOD antisense-transfected SCC cells into the subcutis of each mouse's back, they slowly multiplied to form tumors sized 1,460 ؎ 70 mm 3 at day 60, while control vector-transfected SCC cells rapidly multiplied, with a mean tumor size of 2,330 ؎ 220 mm 3 . Inversely, mice in the Mn-SOD antisense group survived longer (mean survival duration 94.4 ؎ 12.7 days) compared to those in the empty vector group (67.3 ؎ 6.8 days). After treatment with 5-FU (5 g/day), PLM (50 g/day), CDDP (10 g/day) and ␥-rays (2 Gy/day), mean survival times were largely prolonged, to 126.3 ؎ 22.7, 123.0 ؎ 22.1, 136.3 ؎ 24.0 and 143.0 ؎ 20.8 days, respectively, while mean survival times in the empty vector group were 91.7 ؎ 14.8, 85.7 ؎ 13.3, 97.5 ؎ 16.0 and 100.7 ؎ 17.1 days, respectively. Immunohistologically, tumors in the Mn-SOD antisense group revealed additional nick end-labeled cells compared to those in the empty vector group. In comparison, strong expression of Bax, Bak and p21 waf1/cip1 and suppressed expression of Bcl-2, Bcl-X L and COX-2 were observed in the Mn-SOD antisense group and the expression pattern of these proteins was the inverse in the empty vector group. The increased expression of these proapoptotic proteins appeared to be p53-independent because p53 protein expression was not increased in the antisense group. These immunohistologic results were supported by Western blotting of each protein. In conclusion, Mn-SOD antisense transfection is advantageous for apoptosis induction of SCC cells by anticancer drugs and ␥-rays through induction of proapoptotic Bcl-2 family proteins and suppression of antiapoptotic protein expression.