目的 分析胃癌患者中多聚腺苷二磷酸核糖聚合酶（PARP）族基因的表達(dá)情況及其與預(yù)后的關(guān)系，體外細(xì)胞實(shí)驗(yàn)研究胃復(fù)春膠囊醇提物（WFCEE）對(duì)胃癌SGC-7901細(xì)胞及PARP表達(dá)的影響。方法 基于TCGA/GTEx/GEO數(shù)據(jù)庫(kù)分析PARP族基因表達(dá)及預(yù)后，蛋白互作網(wǎng)絡(luò)分析PARP族基因的主要生物功能，并采用MCODE聯(lián)合cytoHubba預(yù)測(cè)核心基因及其作用通路。將SGC-7901細(xì)胞與WFCEE（10、20、50 μg·mL^-1）共孵育，采用CCK-8細(xì)胞增殖與活性檢測(cè)試劑盒檢測(cè)細(xì)胞活力，流式細(xì)胞術(shù)Annexin V/PI雙染色檢測(cè)細(xì)胞凋亡，Western blotting法檢測(cè)PARP及凋亡相關(guān)蛋白表達(dá)情況。結(jié)果 與正常組比較，胃癌患者PARP1、PARP4、PARP6、PARP9等基因表達(dá)有顯著性差異；K-M曲線生存預(yù)后分析顯示PARP平均表達(dá)量低組患者生存率高、中位生存時(shí)間更長(zhǎng)。蛋白互作分析顯示PARP家族主要與蛋白質(zhì)ADP-核苷酸化、戊糖基團(tuán)轉(zhuǎn)移酶活性、糖基團(tuán)轉(zhuǎn)移酶活性、染色體上蛋白質(zhì)定位、正或負(fù)向調(diào)節(jié)DNA代謝過(guò)程等過(guò)程相關(guān)，其中PARP1、PARP2、PARP3、PARP9、PARP10、PARP12、PARP14為核心基因，調(diào)節(jié)堿基切除修復(fù)、細(xì)胞凋亡、壞死性凋亡等信號(hào)通路。與對(duì)照組比較，WFCEE可時(shí)間、劑量相關(guān)性地抑制SGC-7901細(xì)胞活力并誘導(dǎo)凋亡（P＜0.05、0.01） ；20、50 μg·mL^-1組PARP蛋白表達(dá)量顯著降低（P＜0.05）；各濃度組cleaved caspase-3、cleaved caspase-9、Bax蛋白表達(dá)量顯著增加（P＜0.01、0.001），Bcl-2蛋白表達(dá)量顯著降低（P＜0.01、0.001）。結(jié)論 PARP在胃癌組表達(dá)與正常組比較存在顯著差異，并且與預(yù)后相關(guān)性顯著，在胃癌臨床應(yīng)用方面有一定的價(jià)值；WFCEE可抑制胃癌細(xì)胞的增殖并誘導(dǎo)其凋亡，其作用機(jī)制可能與Bax/Bcl2-caspase3/9-PARP路徑相關(guān)。

Objective To analyze the relationship between the expression of polyadenosine diphosphate-ribose polymerase (PARP) family genes and prognosis, and to verify the intervention of Weifuchun Capsules ethanol extract (WFCEE) on gastric cancer SGC- 7901 cells and PARP expression through cell in vitro experiments. Methods The expression and prognosis of PARP family genes were analyzed based on TCGA/GTEx/GEO database, protein interaction network analysis of the main biological functions of PARP family genes and using MCODE combined with cytoHubba to predict core genes and their pathways. Gastric cancer SGC-7901 cells were co-incubated with WFCEE (10, 20, and 50 μg·mL^-1) , cell viability was detected by Cell Counting Kit-8 (CCK-8) cell proliferation and activity detection kit, and cells were detected by flow cytometry Annexin V/PI double staining apoptosis, Western blotting method to detect the expression of PARP and related apoptosis proteins. Results There were significant differences in the expressions of PARP1, PARP4, PARP6, and PARP9 in gastric cancer group compared with control group. K-M curve survival prognosis analysis showed that patients with low average expression of PARP had a higher survival rate and a longer median survival time. Protein interaction analysis shows that the PARP family is mainly related to protein ADP-nucleotide, pentose group transferase activity, sugar group transferase activity, protein localization on chromosome, positive or negative regulation of DNA metabolism and other processes, among which PARP1/PARP2/PARP3/ PARP9/PARP10/PARP12/PARP14 are core genes, regulating base excision repair/apoptosis/ necroptosis and other signaling pathways. Experiments proved that, Compared with control group, WFCEE can inhibit the viability of SGC-7901 cells and induce apoptosis of SGC-7901 cells in a time- and dose-dependent manner (P < 0.05, 0.01, and 0.001). Western blotting shows that, WFCEE can down-regulate the expression of PARP and up-regulate the expressions of cleaved caspase-3, cleaved caspase-9, and Bax (P < 0.05, 0.01, and 0.001), and increase the expression of Bcl-2 (P < 0.01 and 0.001). Conclusion Compared with normal group, the expression of PARP in the gastric cancer group is significantly different and has a significant relationship with the prognosis, which has certain value in the clinical application of gastric cancer. Experiments have proved that WFCEE can inhibit the proliferation of gastric cancer cells and induce their apoptosis, and its mechanism of action is speculated to be the Bax/Bcl2-caspase3/9-PARP pathway.

浙江省科技計(jì)劃項(xiàng)目（中藥二次開(kāi)發(fā)研究——以臨床價(jià)值和質(zhì)量提升為導(dǎo)向的“胃復(fù)春”大品種二次開(kāi)發(fā)研究-2022C03131）