补肾法对化疗所致骨髓抑制荷瘤小鼠细胞周期CyclinD-CDK4/6 信号途径的双重调控作用及其机制
ual control of kidney nourishing therapy on CyclinD-CDK4/6 signal pathway of cell reproductive cycles in Lewis-bearing mice with cyclophosphamide-induced mye1osuppression.
本研究探讨补肾法对化疗所致骨髓抑制荷瘤小鼠细胞周期的双重调控作用及其机制。采用Lewis肺癌荷瘤小鼠，30只小鼠随机分为空白组、模型组和治疗组。除空白组外，腹腔注射环磷酰胺制作骨髓抑制模型。治疗组用40g／(kgod)双黄升白颗粒治疗6 d，检测血常规、骨髓及肿瘤细胞周期，以实时荧光定量PCR（RT-qPCR）reverse transcription quantitative real-time PCR ( RT-qPCR检测CyclinD-CDK4/6 上游激活信号C-myc、CDC25A，上游抑制信号p16INK4a及p15INK4b，以及CyclinD-CDK4/6所激活的下游信号Rb、pRb、E2F的表达，并以western blot法进行验证。研究发现双黄升白颗粒能促进骨髓细胞跨过G0/G1期进入S 期，加速细胞周期的进程，升高PI。同时，抑制肿瘤细胞跨过G0/G1期进入S 期，降低PI，模型组骨髓组织的C-myc、CDC25A、Rb、pRb、E2F的表达均高于空白组(P<0.05)。肿瘤组织C-myc、CDC25A表达均高于空白组(P<0.05)。治疗组C-myc、CDC25A的表达均高于模型组及空白组(P<0.05)。肿瘤组织C-myc、CDC25A的表达均低于模型组及空白组(P<0.05)。说明双黄升白颗粒对化疗所致骨髓抑制Lewis肺癌荷瘤鼠的细胞周期具有双向调控作用，其机制可能与调控细胞周期CyclinD-CDK4/6上游激活信号C-myc、CDC25A及其所激活的下游信号Rb、pRb、E2F的表达有关。
Background:This study investigated the dual control mechanism of kidney nourishing therapy modulating the cell cycle in Lewis-bearing mice with cyclophosphamide induced myelosuppression. Methods: Thirty Lewis-bearing mice were randomly grouped into an untreated group, control group, and treated group. Both treated and untreated groups were intraperitoneally injected with cyclophosphamide to produce a myelosuppression model. Mice in the treated group were fed with theShuanghuangShengbaigranule (40 g/day) for 6 consecutive days. Standard blood tests and the count of bone marrow nuclear cells were performed, and the cell reproductive cycles of bone marrow and tumorswere measured in these mice. In addition, the western blot approach was used to measure the upstream activating signals of CyclinD-CDK4/6 such as c-Myc and CDC25A, the upstream suppression signals such as p16INK4a and p15INK4b, and the expression of downstream activated signals such as Rb, pRB, and E2F. All of the tested results were validated by reverse transcription quantitative real-time polymerase chain reaction. Results: The results showed that the ShuanghuangShengbaigranule could elevate the count of leukocyte and bone marrow nuclear cells of Lewis-bearing mice with cyclophosphamide induced myelosuppression. It could also stimulate bone marrow cells to move from G0/G1 phases to S phase, accelerating the progress of the cell reproductive cycle and increasing the cell proliferation index. Simultaneously, the ShuanghuangShengbaigranule could also suppress cancer cells moving from G0/G1 phase to S phase, reducing the proliferation index. The tumor weight of Lewis-bearing mice in the treated group was much less than those of the control group. Expression levels of c-Myc, CDC25A, Rb, pRb, and E2F of bone marrow in ShuanghuangShengbaigranule-treated mice was higher compared to the control group, whereas they were lower in the cancer cells. Conclusion: The experimental results demonstrate that the ShuanghuangShengbaigranule has dual control on the cell reproductive cycles in cancer cells and bone marrow nuclear cells in Lewis-bearing mice.
顾贤、徐振晔
医药卫生理论基础医学肿瘤学
补肾法yclinD-CDK4/6-myc25Ap16INK4ap15INK4bRbpRbE2F
kidney nourishing therapyCyclinD-CDK4/6c-MycCDC25Ap16INK4ap15INK4bRbpRbE2F
顾贤,徐振晔.补肾法对化疗所致骨髓抑制荷瘤小鼠细胞周期CyclinD-CDK4/6 信号途径的双重调控作用及其机制[EB/OL].(2012-12-25)[2025-08-02].http://www.paper.edu.cn/releasepaper/content/201212-758.点此复制
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