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

被引：35

作者：

Ueta, E ^{[1
]}

Yoneda, K ^{[1
]}

Kimura, T ^{[1
]}

Tatemoto, Y ^{[1
]}

Doi, S ^{[1
]}

Yamamoto, T ^{[1
]}

Osaki, T ^{[1
]}

机构：

[1] Kochi Med Sch, Dept Oral Surg, Kochi 7838505, Japan

来源：

INTERNATIONAL JOURNAL OF CANCER | 2001年 / 94卷 / 04期

关键词：

Mn-SOD antisense; squamous cell carcinoma; reactive oxygen intermediates; Bcl-2 family proteins; COX-2; p21;

D O I：

10.1002/ijc.1513

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

ROIs and their scavengers are associated with apoptosis induction by anticancer drugs and gamma -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 gamma -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 mug/day), PLM (50 mug/day), CDDP (10 mug/day) and gamma -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 gamma -rays through induction of proapoptotic Bcl-2 family proteins and suppression of antiapoptotic protein expression. (C) 2001 Wiley-Liss, Inc.

引用

页码：545 / 550

页数：6

共 63 条

[41]

OBERLEY TD, 1993, FREE RADICALS AGING, P248

[42] LOW-LEVELS OF REACTIVE OXYGEN SPECIES AS MODULATORS OF CELL-FUNCTION [J].