[關(guān)鍵詞]
[摘要]
目的 研究生脈注射液對(duì)不同化療藥物的增敏作用,并初步探討其機(jī)制。方法 通過MTT法測(cè)定生脈注射液對(duì)于不同臨床典型化療藥物的增敏效果,通過流式細(xì)胞術(shù)測(cè)定生脈注射液聯(lián)合表阿霉素對(duì)人肝癌HepG-2細(xì)胞周期和細(xì)胞凋亡的影響;RT-PCR方法檢測(cè)生脈注射液對(duì)于多藥耐藥基因MDR-1表達(dá)的影響。結(jié)果 生脈注射液(30 μL/mL)聯(lián)合吉西他濱、順鉑、紫杉醇和表阿霉素對(duì)不同腫瘤細(xì)胞A549、SGC-7901、MCF-7和HepG-2具有藥物增敏作用,其中聯(lián)合表阿霉素作用效果最為顯著,使肝癌HepG-2細(xì)胞對(duì)表阿霉素的敏感性提高16倍。流式細(xì)胞儀和RT-PCR結(jié)果顯示,生脈注射液(30 μL/mL)不影響腫瘤細(xì)胞的周期和凋亡,但與表阿霉素聯(lián)用在促進(jìn)表阿霉素改變HepG-2細(xì)胞周期和誘導(dǎo)凋亡的同時(shí),能夠降低MDR-1基因的表達(dá)水平。結(jié)論 生脈注射液聯(lián)合不同化療藥物對(duì)多種腫瘤細(xì)胞均有明顯的增敏作用,其作用機(jī)制與降低MDR-1基因表達(dá)水平及其編碼的具有藥物外排作用的P-糖蛋白的表達(dá)有關(guān)。
[Key word]
[Abstract]
Objective To investigate the chemo-sensitivity enhancing effect and its major active mechanism of Shengmai Injection (SMI). Methods MTT assay was used to determine the chemo-sensitivity enhancing activity of SMI combined with various current- used chemotherapeutic drugs. Flow cytometry was conducted to determine the effect of Epirubicin combined with SMI on the cell cycle distribution and apoptotic cell death, and the mRNA expression level of MDR-1 gene was determined by RT-PCR. Results SMI (30 μL/mL) combined with gemcitabine, cisplatin, paclitaxel, and Epirubicin exihibited the potent antiproliferative effects on human lung carcinoma A549, gastric carcinoma SGC-7901, breast carcinoma MCF-7, and hepatocellular carcinoma HepG-2 cell lines, respectively. SMI showed the most significant enhancing effects on HepG-2 cells in combination with Epirubicin, and the sensitivity of HepG-2 to Epirubicin was increased by 16 fold. Whereas SMI (30 μL/mL) alone did not affect the cell cycle distribution and apoptosis of HepG-2 cells, it enhanced the cellular responses when combined with Epirubincin together with a down-regulated mRNA level of MDR-1 gene. Conclusion SMI combined with the different chemotherapeutic drugs could enhance the sensitivity of cancer cells significantly via down-regulating the mRNA expression level of MDR-1 and the expression of P-glucoprotein with the excretion of drugs.
[中圖分類號(hào)]
[基金項(xiàng)目]
遼寧省自然科學(xué)基金資助項(xiàng)目(20102295)