BACKGROUND:12-lipoxygenase(12-LOX) has been reported to be an important gene in cancer cell proliferation and survival,and tumor metastasis.However,its role in hepatocellular carcinoma(HCC) cells remains unknown.METHODS:Expression of 12-LOX was assessed in a diethylnitrosamine-induced rat HCC model,and in SMMC-7721,HepG2 and L-02 cells using immunohistochemical staining and reverse transcriptase-polymerase chain reaction(RT-PCR).GST-π and Ki-67 were determined in vivo by immunohistochemical staining.Apoptosis was evaluated by TUNEL assay.Cell viability and apoptosis were determined by MTT assay and flow cytometry,respectively.Apoptosis-related proteins in SMMC-7721 and HepG2 cells were detected by Western blotting.RESULTS:Immunohistochemical staining and RT-PCR showed that 12-LOX was over-expressed in rat HCC and two HCC cell lines,while the expression was inhibited by baicalein,a specific inhibitor of 12-LOX.Baicalein inhibited cell proliferation and induced apoptosis in rat HCC and both cell lines in a dose-and time-dependent manner.Our in vivo study demonstrated that baicalein also reduced neoplastic nodules.Mechanistically,baicalein reduced Bcl-2 protein expression coupled with a slight increase of the expression of Bax and activation of caspase-3.Furthermore,baicalein inhibited the activation of ERK-1/2(phosphorylated).Interestingly,the effects of baicalein were reversed by 12(S)-HETE,a metabolite of 12-LOX.CONCLUSIONS:Inhibition of 12-LOX leads to reduced numbers of HCC cells,partially caused by increased apoptosis.12-LOX may be a potential molecular target for HCC prevention and treatment.
Xi-Ming Xu,Guang-Jin Yuan,Jun-Jian Deng,Hong-Ting Guo,Miao Xiang,Fang Yang,Wei Ge and Shi-You Chen Cancer Center, Renmin Hospital of Wuhan University, Wuhan 430060, China
Objective: The aim of the study was to evaluate the efficacy and safety of cytokine-induced killer(CIK) cell combined with transcatheter arterial chemoembolization(TACE) therapy in the treatment of hepatocellular carcinoma(HCC).Methods: Randomized controlled trials(RCTs) on CIK cells combination with TACE based-therapy were identified by electronic searches in the Cochrane Library, MEDLINE, Pubmed, Wanfang, VIP, CNKI and other electronic databases. We included any RCTs evaluating CIK cell combination with TACE for the treatment of hepatocellular cancers. The quality of RCTs meeting inclusion criteria was evaluated and data on short-term and long-term curative effects, quality of life, liver function and immunologic function were extracted. For quantitative data, we conducted meta-analysis with ReMan 5.1 software and the GRADE System was used to rate the level of evidence and strength of recommendation. For qualitative data, data mainly adopted descriptive methods. Results: The 9 RCTs involving 870 cases meeting the inclusion criteria were included. The meta-analysis showed significant survival benefit on 0.5-year survival rate(RR = 1.51, 95% CI, 1.35-1.69, P < 0.00001) in favor of CIK based therapy. This effect was consistent at other prospective dates, including 1-year survival rate(RR = 2.30, 95%CI, 1.94-2.72, P < 0.00001), 2-year survival rate(RR = 7.03, 95% CI, 3.83-12.91, P < 0.0001). Meanwhile, the CIK-based group also demonstrated a significantly prolonged time-to-progression(TTP)(SD = 1.62, 95% CI, 1.30-1.94, P < 0.0001) and overall survival(OS)(SD = 20.6, 95% CI, 20.2-21.18, P < 0.0001). Moreover, a favored response rate(RR = CR + PR)(RR =2, 95% CI, 1.65-2.43, P < 0.00001) and the quality of life improvement rate(KPS)(RR = 1.76, 95% CI, 1.26-2.45, P = 0.0008)were also observed in patients receiving CIK cells and TACE therapy. Furthermore, patients in the CIK group showed lower AFP(SD = -165.23, 95% CI, -178.51 - -151.94, P < 0.00001), ALT(SD = -33.14, 95% CI, -40.30 - -36.37, P < 0.00001),and AST(SD = -1
Biao ChenXiming XuMiao XiangJiao YangTingting YuYi Hu
Objective: Epithelial-mesenchymal transition (EMT) is a critical early event for the invasion and metastasis of many carcinomas. In the present study, we examined EMT markers in the residual cancer cells of hepatocellular carcinoma (HCC) after radiotherapy. Methods: Eight patients with large HCC who underwent hepatectomy with preoperative radiothera- py were studied. The expressions of E-cadherin and vimentin were determined immunohistochemically in the residual cancer cells of HCC following radiotherapy, and also in the pre-radiotherapy biopsy cancer cells. Results: Histological analysis showed that some residual cancer cells of HCC displayed an elongated spindle or fibroblast-like shape. The expression of E- cadherin was markedly reduced or negative in the spindle residual cancer cells, but the expression of vimentin significantly in- duced. However, the above changes were not found in the pre-radiotherapy biopsy cancer cells. Conclusion: EMT is induced in the residual cancer cells of HCC following radiotherapy, which may facilitate the systemic dissemination of cancer cells.
Ximing XuJunjian DengGuangjin YuanMiao XiangBiao ChenJiao YangYiqiao ZhangLei ShiZuguo Li
