Gliomas are the most common and lethal primary tumors of the central nervous system (CNS). Despite current rigorous treatment protocols, effect of chemotherapy has failed to improve patient outcome significantly. Curcumin is a potent antioxidant that possesses both anti-inflammatory and anti-tumor activities, can suppress the initiation, promotion, and metastasis of different tumors. Its anti-tumor properties in various cancer models and negligible toxicity in normal cells make it a promising chemotherapeutic candidate. But the effect and the molecular mechanism of curcumin on gliomas are still recognized limitedly. The goal of the study is to elucidate the inhibitory effect and possible mechanisms of curcumin on glioma. After the treatment of curcumin, glioma cells U251 growth in vitro were significantly inhibited in a dose-dependent manner, and the low dose of curcumin induced G2/M cell cycle arrest. The high dose of curcumin not only enhanced G2/M cell cycle arrest, but also induced S phase of cell cycle arrest. But no obvious pre-G1 peak was observed at the different doses of curcumin. Genome DNA electrophoresis further confirmed that no DNA ladder was formed after the treatment of curcumin in U251 cells. Results of Western blot analysis demonstrated that ING4 expression was almost undetectable in U251 cells, but significantly up-regulated during cell cycle arrest induced by curcumin, and p53 expression was up-regulated followed by induction of p21 WAF-1/CIP-1 and ING4. The results demonstrate that curcumin exerts inhibitory action on glioma cell growth and proliferation via induction of cell cycle arrest instead of induction of apoptosis in a p53-dependent manner, and ING4 possibly is in part involved in the signal pathways.
Colorectal cancer (CRC) displays a predilection for metastasis to liver. Although stromal cell-derived factor-1 (SDF-1)/CXCR4 plays an important role in the liver metastasis, the molecular mechanism still remains obscure. We previously reported that integrin αvβ6 was implicated in the progression of CRC. However, no data are currently available on the cross talk between CXCR4 and αvβ6. In the present study, we first demonstrated the cross talk between CXCR4 and αvβ6 and their role in liver metastasis of CRC. We analyzed 159 human CRC samples and found that expression of CXCR4 and αvβ6 was significantly associated with liver metastasis, and interestingly expression of αvβ6 significantly correlated with expression of CXCR4. Both CXCR4 and αvβ6 were highly expressed in metastatic CRC cell lines HT-29 and WiDr, whereas both of them were exiguous in non-metastatic cell line Caco-2. Furthermore, inhibition of αvβ6 significantly decreased SDF-1α-induced cell migration in vitro. SDF-1/CXCR4 could upregulate αvβ6 expression through phosphorylation of ERK and activation of Ets-1 transcription factor. In conclusion, we demonstrate that SDF-1/CXCR4 induces directional migration and liver metastasis of CRC cells by upregulating αvβ6 through ERK/Ets-1 pathway. These data support combined inhibition of CXCR4 and αvβ6 to prevent development of liver metastasis of CRC.
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