新穎化合物Gavin 08抑制人類多型性神經膠質母細胞瘤癌幹細胞之增殖與存活

Abstract

多型性神經膠質母細胞瘤（glioblastoma multiforme, GBM）是最常見的原發性腦瘤，它的高度侵略性使GBM成為預後不良以及復發率高的疾病。傳統的治療為手術輔以放射線及化療為主，但並無法有效根治。目前主要化療藥物Temozolomide (TMZ)在初期可以有效的抑制腦癌細胞的存活率，但因病人常對TMZ產生抗藥性，因此科學家們還在積極尋找其他具有療效的化療藥物。已經有許多研究指出，在癌細胞中之癌幹細胞（cancer stem cells, CSCs）具有特殊蛋白質通道能將化療藥物排出細胞外，對癌症的抗藥性及復發都有很大的關聯性。為了找出可以有效抑制腦癌幹細胞生長的藥物，我們檢測吲哚類的化合藥物是否能夠抑制腦癌類癌幹細胞的增殖。結果顯示Gavin 08可以有效降低腦癌類幹細胞的增殖能力使細胞週期停滯，並且促進細胞凋亡。因此，我們認為Gavin 08可以降低腦癌細胞的增殖與存活，具成為新穎化療藥物的潛力。Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor. Its aggressiveness makes it a malignant disease with poor prognosis and high recurrence. Neither surgical resection nor traditional chemotherapeutic drugs are effective treatments for this disease., The major chemotherapy drug is Temozolomide (TMZ) currently. Although TMZ effectively inhibits the survival rate of glioblastoma cell line in the beginning of the treatment, patients often develop drug resistance soon. Therefore, scientists constantly search for new chemotherapeutic drugs. Many studies have reported that the cancer stem cells (CSCs) in the tumor mass have the special protein channels that can excrete chemotherapeutic drugs out of the cancer stem cell. Thus, CSCs may have strong correlation with cancer recurrence and drug resistance. To screen new therapeutic compounds that effectively inhibit CSCs of GBM, we examined the proliferation inhibition ability of indole compounds for GBM. The results revealed that the chemical compound, Gavin 08, can reduce the cell proliferation and promote the apoptosis of GSCs. In summary, Gavin 08 may be a potential novel chemotherapeutic drug for targeting glioblastoma stem cell.