|摘要: ||肺癌是男性和女性的癌症死亡原因中最常見的一種，其可分為小細胞肺癌和非小細胞肺癌。肺癌的形成和侵襲是一個多步驟的過程，其中涉及癌細胞與鄰近周圍基質間的多種蛋白交互作用，包括基質金屬蛋白酶（matrix metalloproteinase, MMP）和組織金屬蛋白酶抑製劑（tissue inhibitor of metalloproteinase, TIMPs）。基質金屬蛋白酶是一種鋅依賴性內肽酶家族，具有切割細胞外基質的能力。MMP家族中的明膠基質金屬蛋白酶，特別是MMP-2和MMP-9，會參與一些病理過程，例如腫瘤細胞轉移和血管新生。許多的侵入性惡性腫瘤，包括肺癌，皆表現大量的MMP相關酵素，例如 MMP-2、MMP-7、MMP-9、TIMP-1等。Tomatidine是由番茄萃取得到的天然固醇類生物鹼。最近的研究發現tomatidine可以降低發炎作用。Tomatidine對癌細胞轉移方面的研究尚不清楚。本實驗室先前的研究發現， tomatidine對人類肺癌細胞A549的侵入作用有明顯的抑制。本論文擬以reverse transcription- PCR (RT-PCR) 探討tomatidine對MMP-2/-9/-7 mRNA表現的影響。結果發現，tomatidine 在40 μM以下的劑量並不會影響A549細胞的增生。在此無細胞毒性的劑量下，tomatidine可抑制A549細胞的侵入作用。Tomatidine可抑制MMP-2/-9/-7 mRNA基因的表現。同時tomatidine 也抑制組織金屬蛋白酶抑製劑TIMP-1的表現。此結果顯示tomatidine 可能藉由抑制MMP-2/-9/-7基因的表現而抑制人類肺癌細胞A549的侵入作用。|
Lung cancer is the most common cause of cancer-related death in men and women and can be divided into small cell lung carcinoma and non-small cell lung carcinoma. Progression and invasion of lung cancer is a multi-step process involving multiple interactions between the tumor and the surrounding stroma mediated by many proteins, such as metalloproteinase (MMP) and tissular inhibitors of metalloproteinase (TIMP). MMP comprise a family of zinc-dependent endopeptidases that have the capacity to cleave extracellular matrix. The subgroup of MMPs known as gelatinases, speciﬁcally gelatinase A (MMP-2) and gelatinase B (MMP-9), have been implicated in the pathological processes that contribute to tumor progression, such as tumor cell invasion and angiogenesis. Many invasive malignant tumors, such as lung cancers, express high levels of MMPs, including MMP-2, MMP-7, MMP-9, and TIMP-1. Tomatidine, isolated from tomato, is a naturally occurring steroidal glycoalkaloid. Recent study demonstrated that tomatidine suppressed inflammation. However, the effect of tomatidine on metastasis of caner cell is still unclear. In our previous study, we demonstrated that tomatidine suppressed invasion of human lung cancer cell A549. In the present study, we aimed to elucidate the effect of tomatidine on the expressions of MMP-2, -9 and -7 by RT-PCR. Results show that treated of tomatidine at concentrations below 40 μM did not affected viability of A549 cells significantly. When treated with non-toxic doses of tomatidine, cell invasion was markedly suppressed. Tomatidine also reduced the expression of MMP-2, -9 and -7. Meanwhile, tomatidine suppressed the expression of TIMP-1. Taken together, these results suggest that tomatidine suppresses the expression of MMP-2 -9 and -7 and may subsequently contribute to the inhibition of invasion of A549 cells.