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1. 福建医科大学附属第一医院肝胆胰外科,福建,福州,350005
2. 福建医科大学附属第一医院消化内科,福建,福州,350005
网络出版:2014-11-13,
纸质出版:2013
移动端阅览
刘国忠,石铮,郭回希. 索拉菲尼、PDTC联用对胰腺癌细胞株PANC-1的作用研究[J]. 中国癌症杂志, 2013, 23(6): 425-431.
刘国忠, 石铮, 郭回希. Interactions sorafenib of and pyrrolidine dithiocarbamate in pancreatic cancer cells[J]. China Oncology, 2013, 23(6): 425-431.
刘国忠,石铮,郭回希. 索拉菲尼、PDTC联用对胰腺癌细胞株PANC-1的作用研究[J]. 中国癌症杂志, 2013, 23(6): 425-431. DOI: 10.3969/j.issn.1007-3969.2013.06.005.
刘国忠, 石铮, 郭回希. Interactions sorafenib of and pyrrolidine dithiocarbamate in pancreatic cancer cells[J]. China Oncology, 2013, 23(6): 425-431. DOI: 10.3969/j.issn.1007-3969.2013.06.005.
背景与目的:多分子靶向药物索拉菲尼(sorafenib)可抑制多种肿瘤细胞增殖并诱导其凋亡,具有广泛生物学活性,但单药治疗胰腺癌效果较差,可能与肿瘤中核转录因子-κB(nuclearfactor-kappa B,NF-κB)通路激活有关,因此有必要寻求联合NF-κB活化抑制剂吡咯烷二硫代氨基甲酸盐(pyrrolidine dithiocarbamate,PDTC)以提高疗效。本研究观测索拉菲尼联合PDTC对体外人胰腺癌细胞株PANC-1的细胞增殖、细胞周期的影响及其对细胞质中NF-κB表达的影响,并探讨其可能的作用机制。方法:以单药不同浓度的索拉菲尼(1.5、3.0、6.0、12.0 μmol/L)、PDTC(10.0、25.0、50.0、100.0 μmol/L)及低浓度联合用药(3.0 μmol/L索拉菲尼+25.0 μmol/L PDTC)进行分组,在用药后24、36、48、72 h,MTT法检测各组对胰腺癌细胞株PANC-1细胞增殖的抑制作用并分别计算出细胞半数抑制浓度(IC
50
);在用药后48 h,流式细胞仪检测各组药物对细胞周期的影响;在用药后48 h,免疫细胞化学方法观察各药物组NF-κB在细胞中表达水平的变化。结果:索拉菲尼和PDTC均能显著抑制胰腺癌细胞株PANC-1的增殖,但单药IC
50
值较高,低浓度联合用药组能显著提高细胞生长抑制率(P0.05)。索拉菲尼、PDTC及低浓度联合用药组细胞均发生G
0
/G
1
期停滞(P0.05),S期细胞减少,低浓度联合用药组效果优于单药组(P0.05)。索拉菲尼诱导NF-κB在胰腺癌PANC-1细胞内表达明显增强,低浓度联合用药组诱导后胰腺癌PANC-1细胞中NF-κB的表达明显减弱(P0.05)。结论:索拉菲尼和PDTC在体外对PANC-1细胞增殖均具有抑制作用,但单药效果不佳。PDTC和索拉菲尼联合应用能明显提高胰腺癌细胞株PANC-1细胞的生长抑制率,并使细胞发生G
0
/G
1
期停滞,其原因可能是PDTC通过抑制NF-κB活化,增强PANC-1细胞对索拉菲尼的敏感性。
Background and purpose: Sorafenib
a multiple targeted agent
can inhibit proliferation and induce apoptosis of diverse tumor cell in vitro. It has extensive biological activities
but the pancreatic cancer effect of monotherapy is poor. This may be related to nuclear factor-kappa
B (NF-κB) pathway activation in cancer. Therefore
it is necessary to combine with Pyrrolidinedithiocarbamate (PDTC
a NF-κB activation inhibitor) to enhance curative effect. To investigate the influences of cell proliferation
cell cycle and expression of NF-κB via their acting on human pancreatic cancer PANC-1
and explore their possible mechanism. Methods: The experiment groups were divided into sorafenib group with different concentrations (1.5
3.0
6.0
12.0 μmol/L)
PDTC group with different concentrations (10.0
25.0
50.0
100.0 μmol/L) and combination group with low concentration (3.0 μmol/L sorafenib +25.0 μmol/L PDTC). The proliferative activity of PANC-1 of each group was measured by MTT assay at different time points of 24
36
48 and 72 h
and the half inhibitory concentration (IC
50
) was calculated
respectively. Cell cycle in each group was detected by flow cytometry instrument after 48 h. The changes of NF-κB expression level in each group were observed by immunocytochemistry after 24 h. Results: Sorafenib and PDTC can significantly inhibit the proliferation of PANC-1
but IC
50
value of the single medicine was higher
combination group with low concentration can significantly increase the cell growth inhibition rate (P0.05). Three groups can induce the cell stagnation at G
0
/G
1
phase (P0.05) and cells at S phase were decreased. The effect of combination group with low concentration was better than the single drug group (P0.05). The NF-κB expression level in sorafenib group was significantly enhanced
while the level in combination group was significantly decreased (P0.05). Conclusion: Sorafenib and PDTC can significantly inhibit the growth of human pancreatic cancer PANC-1 cells in vitro
but the effect of one drug is unsatisfactory. PDTC combined with sorafenib significantly improve the inhibition rate of the proliferation of human pancreatic cancer PANC-1
and induce the cell stagnation at G
0
/G
1
phase. This may relate to inhibit
the activation of NF-κB by PDTC and enhance the sensitivity of PANC-1 cells to sorafenib.
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