Evaluation of the glioma growth and angiogenic effects of leptin in brain slice model

• Main Authors: Chia-Chen Chang, 張家禎
• Other Authors: Yi-Lo Lin
• Format: Others
• Language: zh-TW
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/67601705081203971617

碩士 === 國立中興大學 === 獸醫病理生物學研究所 === 102 === Malignant glioma is the most aggressive type of brain tumors, with high recurrence rate. Despite of aggressive therapy, there is limited effect on the survival time of these patients and the prognosis. Until now, only few agents are approved for treating glioma. Therefore new therapeutic targets are needed. Leptin is predominantly secreted from adipocytes. During the past few years, it has been demonstrated that Leptin induces cell growth. Besides, Leptin and its receptor, ObR, are over-expressed in many malignant tumors. Therefore, Leptin might be associated with tumor cell growth and tumor malignancy. We hypothesized that Leptin promotes glioma growth and tumor angiogenesis and therefore by inhibiting Leptin might decrease tumor growth and angiogenesis. In the first part of this study, we established a C6 glioma model by using brain slice culture system, and measured tumor size in 1, 24, 48, and 72 hrs. No significant difference in the tumor size was observed between these time points. In the second part of this study, Leptin, JAK pathway inhibitor (AG490), or Leptin receptor (ObR) was administrated. Tumor growth were evaluated on 24 and 72 hrs and angiogenesis were evaluated on 72 hrs. Results showed that in both 24 and 72 hrs, there was no significant difference in the tumor size in Leptin group comparing to C6 group, but in both ObR group AG490 group the tumor size decreased significantly. Although the inhibition of Leptin can decrease tumor size, the margin of tumor was irregular and tumor cells were dispersed. No significant difference in the vessel density and the length of vessels around tumor mass was observed in Leptin group and AG490 group comparing to C6 group. In contrast, in ObR group the vessel density was significant lower than the C6 group, but difference of the total length of vessels did not reach the significance. In conclusion, this study demonstrated that by inhibiting Leptin reduced tumor volume and tumor angiogenesis, but the tumor margin was ill defined. This effect might associate with cell migration and deserves further study.