Anti-cancer effect of bio-reductive drug β-lapachon is enhanced by activating NQO1 with heat shock
Anti-cancer effect of bio-reductive drug β-lapachon is enhanced by activating NQO1 with heat shock
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热休克激活NQO1增强生物还原药物β-lapachon的抗癌作用
DOI：
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发表时间：
2008
影响因子：
3.1
通讯作者：
H. Park
中科院分区：
文献类型：
--
作者：
C. W. Song;J. J. Chae;E. Choi;Tae;Chulhee Kim;B. Lim;H. Park
目的：通过NAD(P)H：醌氧化还原酶（NQO1）介导抗癌药物β-拉帕酮（β-lap）的生物还原/活化。我们探讨了利用低温热疗通过上调NQO1表达来增强β-lap抗癌作用的可行性。方法：采用Western blot法检测C3H小鼠FSaII纤维肉瘤和A549人肺癌细胞中NQO1的表达，并对水浴加热后不同时间细胞进行免疫染色。采用克隆细胞存活法测定细胞对加热、β-lap和两者的敏感性。采用水浴加热42°C 1 h、加热24 h后小鼠腹腔注射β-lap或腹腔注射β-lap，研究C3H小鼠右后肢FSaII肿瘤的生长情况。结果：42℃加热1 h可显著提高NQO1在癌细胞中的表达，在加热后8-24 h达到最大表达量。癌细胞对β-lap处理的敏感性逐渐增加，直到加热后24小时，这很可能是由于NQO1表达的增加。在42℃下加热FSaII肿瘤1 h，在肿瘤加热24 h后腹腔注射50 mg/kg β-lap治疗宿主小鼠，其抑制肿瘤生长的效果远远优于单独加热或单独β-lap治疗。结论：低温热休克可提高肿瘤细胞NQO1的表达，从而显著提高肿瘤细胞对生物还原药物β-lap的体外和体内敏感性。
Purpose: Bio-reduction/activation of anti-cancer drug β-lapachone (β-lap) is mediated by NAD(P)H: Quinone oxidoreductase (NQO1). We investigated the feasibility of using mild temperature hyperthermia to increase the anti-cancer effect of β-lap by up-regulating NQO1 expression. Methods: NQO1 expression in FSaII fibrosarcoma of C3H mice and A549 human lung cancer cells was evaluated with Western blot analysis and immunostaining of cells at different times after water-bath heating. Clonogenic cell survival method was used to determine the sensitivity of cells to heating, β-lap, and in combination. The growth of FSaII tumors in the right hind legs of C3H mice was studied after heating the tumors at 42°C for 1 h with water bath, an i.p. injection of β-lap to host mice or an i.p. injection of β-lap 24 h after heating the tumors. Results: Heating at 42°C for 1 h significantly increased the expression of NQO1 in the cancer cells with a maximum increase occurring 8–24 h after heating. The sensitivity of cancer cells to β-lap treatment progressively increased until 24 h after heating most likely due to the increase in NQO1 expression. Heating the FSaII tumors at 42°C for 1 h and treating the host mice with an i.p. injection of 50 mg/kg β-lap 24 h after the tumor heating was far more effective than heating alone or β-lap treatment alone to suppress the tumor growth. Conclusion: Mild temperature heat shock elevates the NQO1 expression in cancer cells, which in turn markedly increases the sensitivity of the cells to the bioreductive drug β-lap in vitro and in vivo.
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影响因子：
11.2
作者：
Bentle, Melissa S.;Reinicke, Kathryn E.;Boothman, David A.
通讯作者：
Boothman, David A.
DOI：
10.1073/pnas.96.23.13369
发表时间：
1999-11-09
影响因子：
11.1
作者：
Li, CJ;Li, YZ;Pardee, AB
通讯作者：
Pardee, AB
影响因子：
4.8
作者：
Choi, Eun K.;Terai, Kaoru;Park, Heon Joo
通讯作者：
Park, Heon Joo
DOI：
--
发表时间：
2000
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
J. Pink;S. Planchon;C. Tagliarino;M. Varnes;D. Siegel;D. Boothman
通讯作者：
J. Pink;S. Planchon;C. Tagliarino;M. Varnes;D. Siegel;D. Boothman
影响因子：
11.2
作者：
Guo, WC;Reigan, P;Ross, D
通讯作者：
Ross, D