Transarterial Infusion Chemotherapy With and Without Embolisation in Hepatocellular Carcinoma Patients: A Systematic Review and Meta-Analysis.

INTRODUCTION: The purpose of this meta-analysis was to compare the efficacy of transarterial chemoembolisation (TACE) and iodised oil infusion chemotherapy without embolisation (TAI) in patients with hepatocellular carcinoma. MATERIALS AND METHODS: We searched for randomised controlled trials, retrospective cohort studies, and two-arm prospective studies that compared the clinical outcomes in patients who received TACE and TAI treatment. Database search was performed through 14 December 2016. Rates of survival and therapy response were compared using odds ratios (OR) with 95% confidence intervals (CI). RESULTS: Survival rates and therapy response rates were similar between patients who received TACE and TAI treatments (pooled OR: 1.278; 95% CI, 0.783 to 2.086, P = 0.327; and pooled OR: 1.502; 95% CI, 0.930 to 2.426, P = 0.096, respectively). CONCLUSION: Our results suggest that treatment intensification by adding embolisation did not increase overall survival and therapy response over TAI in patients with hepatocellular carcinoma.

Baicalein inhibits the invasion and metastatic capabilities of hepatocellular carcinoma cells via down-regulation of the ERK pathway.

Baicalein, a widely used Chinese herbal medicine, has historically been used in anti-inflammatory and anti-cancer therapies. However, the anti-metastatic effect and molecular mechanism(s) of baicalein on hepatocellular carcinoma (HCC) remain poorly understood. Therefore, the purpose of this study was to assess the anti-metastatic effects of baicalein and related mechanism(s) on HCC. Based on assays utilized in both HCC cell lines and in an animal model, we found that baicalein inhibited tumor cell metastasis in vivo and in vitro. Furthermore, after treatment with baicalein for 24 hours, there was a decrease in the levels of matrix metalloproteinase-2 (MMP-2), MMP-9 and urokinase-type plasminogen activator (u-PA) expression as well as proteinase activity in hepatocellular carcinoma MHCC97H cells. Meanwhile, the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 were increased in a dose-dependent fashion. Moreover, baicalein treatment dramatically decreased the levels of the phosphorylated forms of MEK1 and ERK1/2. MEK1 overexpression partially blocked the anti-metastatic effects of baicalein. Combined treatment with an ERK inhibitor (U0126) and baicalein resulted in a synergistic reduction in MMP-2, MMP-9 and u-PA expression and an increase in TIMP-1 and TIMP-2 expression; the invasive capabilities of MHCC97H cells were also inhibited. In conclusion, baicalein inhibits tumor cell invasion and metastasis by reducing cell motility and migration via the suppression of the ERK pathway, suggesting that baicalein is a potential therapeutic agent for HCC.

Baicalein induces apoptosis via a mitochondrial-dependent caspase activation pathway in T24 bladder cancer cells.

Recurrence of bladder cancer following transurethral resection of bladder tumor (TURBt) is an obstacle in clinical management. In the current study, we investigated the antitumor activity of baicalein, a Chinese herbal medicine, against T24 bladder cancer cells in vitro. Baicalein inhibited growth and caused G1/S arrest of the cell cycle in the T24 cells. Moreover, baicalein induced apoptosis via loss of mitochondrial transmembrane potential (ΔΨm), release of cytochrome c and activation of caspase-9 and caspase-3. Baicalein inhibited Akt phosphorylation, downregulated Bcl-2 expression and upregulated Bax expression, which in turn increased the ratio of Bax/Bcl-2. Our results demonstrate that baicalein repressed growth inhibition and induced apoptosis via loss of ΔΨm and activation of caspase-9 and caspase-3 in T24 bladder cancer cells, which indicates that baicalein may be an effective agent in the clinical management of bladder cancer.

Preferential inhibition of hepatocellular carcinoma by the flavonoid Baicalein through blocking MEK-ERK signaling.

Baicalein is a purified flavonoid extracted from the roots of Scutellaria baicalensis or Scutellaria radix. Although previous studies have suggested that Baicalein possesses an in vitro anti-hepatocellular carcinoma activity, its in vivo effects and mechanisms of action are still not completely understood. In this study, Baicalein at concentrations of 40-120 µM exhibited significant cytotoxicity to three hepatocellular carcinoma (HCC) cell lines but marginal cytotoxicity to a normal liver cell line in vitro. Compared to a standard chemotherapy drug, 5-fluorouracil (5-FU), Baicalein had greater effect on HCC cells but less toxicity on normal liver cells. Treatment with Baicalein dramatically reduced mitochondrial transmembrane potential, and activated caspase-9 and caspase-3. Blockade of Baicalein-induced apoptosis with a pan-caspase inhibitor partially attenuated Baicalein-induced growth inhibition in HCC. Baicalein treatment significantly inhibited tumor growth of HCC xenografts in mice. Induction of apoptosis was demonstrated in Baicalein-treated xenograft tumors by the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Furthermore, Baicalein treatment dramatically decreased the levels of phosphorylation of MEK1, ERK1/2 and Bad in vitro and in vivo. Overexpression of human MEK1 partially blocked Baicalein-induced growth inhibition. Consequently, these findings suggest that Baicalein preferentially inhibits HCC tumor growth through inhibition of MEK-ERK signaling and by inducing intrinsic apoptosis.

Chrysanthemum indicum ethanolic extract inhibits invasion of hepatocellular carcinoma via regulation of MMP/TIMP balance as therapeutic target.

Hepatocellular carcinoma (HCC) is an aggressive cancer with a dismal outcome largely due to metastasis and postsurgical recurrence. Thus, the inhibition of invasion and metastasis is of great importance in its therapies. Medicinal plants or ethnopharmacology used in folklore medicine continue to be an important source of discovery and development of novel or potential therapeutic agents for treatment of cancer. Chrysanthemum indicum, one of the medicinal plants or ethnopharmacology, is being used for treatment of many diseases including cancer. However, this plant molecular mechanisms underlining the anti-metastatic effects have not been well documented. In this study, Chrysanthemum indicum ethanolic extract (CIE) significantly suppressed proliferation and invasion of MHCC97H cells, one of the HCC cell lines with high metastatic potential, in a dose-dependent manner. CIE markedly decreased MMP-2 and MMP-9 expression, increased simultaneously TIMP-1, and TIMP-2 expression further restoring their balance in the cancer cells. The present study indicates that CIE reduced MHCC97H cell metastatic capability, in part at least, through decrease of the MMP expression, simultaneous increase of the TIMP expression, further restoring their balance as therapeutic target in HCC. It is suggested that Chrysanthemum indicum is a potential novel therapeutic medicinal plant for treatment of HCC or cancer invasion and metastasis.