紫杉醇诱导成骨肉瘤细胞凋亡及Caspase-6基因对成骨肉瘤细胞的凋亡诱导作用
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摘要
紫杉醇是新型广谱高活性抗癌药，其独特的作用机理是促进微管聚合并
稳定微管结构，诱导肿瘤细胞凋亡。本文应用形态学观察，MTT分析法，
DNA梯状电泳，流式细胞术检测术，研究了紫杉醇对成骨肉瘤细胞系
SOSP-9607的细胞毒效应。结果发现，紫杉醇对SOSP-9607的细胞毒作用
主要是通过诱导凋亡实现的。并且证实紫杉醇在体外对成骨肉瘤细胞株
SOSP-9607有较强的杀伤作用。
哺乳动物体内发现了多种半胱氨酸蛋白酶，这些结构特点相似的酶构成
了一个蛋白酶家族，称之为Caspase家族。它在细胞凋亡过程中起着重要作
用，根据Caspase在级联反应中的作用和活化的先后，Caspase的14个成员分
为启动性和效应性Caspase。启动性Caspase在细胞凋亡信号和调节因子的作
用下首先活化，再激活效应性Caspase、活化的效应性Caspase作用于相应的
箩四军医大学博士学位论文
底物导致凋亡。Caspase－6是一种效应Caspase分子，研究表明o甲ase的表
达水平与肿瘤组织细胞凋亡有关。
本实验应用 RT—PCR方法检测了成骨肉瘤细胞株 SOSP—9607 中
Caspase－6的表达，发现其无表达。构建T Caspase七转基固腺病毒叫6载
体，月质体法转染 SOSP—9607，RT—PCR法证实转染后 SOSP—9607 中
Caspase表达明显。进一步通过MTT法W实转染Ca叩ase－6对SOSP－9607
的生长有抑制作用，通过形态学观察及DNA电泳证实这种作用主要是通过
促进细胞凋亡而实现的。
Paclitaxel is new broad-spectrum anti-tumor drug, which has a unique
mechanism of promoting the stability of microtube and inducing apoptosis. In the
present study, the cytotoxic effect of paclitaxel on human osteosarcoma cell line
SOSP-9607 was examined by MTT assay, morphological observation, gel
electrophoresis of DNA, and cell morphology. The results showed that the
cytotoxic effect of paclitaxel on SOSP-9607 cell is achieved by inducing
apoptosis. Also, the killing effect of paclitaxel toward SOSP-9607 cell line was
conffrmed in vitro.
A group of caspase (cycteinyl asparate-specifi protease) was found in mammal.
With similar structure, they constitute a proteases family and play a very
important role in the process of cell apoptosis. Fourteen members of this family
4
could be classified into two groups: initiators and effectors. Caspases exist in an
inactive form in normal cells. When apoptotic signal has been sent in, they will
be cleaved and activated. After initiators have been activated, effectors can be
activated. Active effectors cleave their substrates after an aspartate residue and
induce apoptosis. Caspase-6 is kind of effectors.
The relationship between the expression level of caspase and the apoptosis
of tumor cell was confirmed by many reports.
In this study, we examined the expression of caspase-6 in the osteosarcoma
line SOSP-9067 by RT-PCR method. Results showed no expression of caspase-6.
We constructed a caspase 6 gene-transfer virus adv5 vectors and transfeced it into
the osteosarcoma line SOSP-9607 by way of lipofection. A high expression of
caspase 6 was identified by RT-PCR after the transfection. The cell survival rate
was assayed by MTT method. The result indicates the caspase 6 may inhibit the
growth of the transfected cell. The morphological observation and gel
electrophoresis of DNA also confirmed the inhibition effect of caspase 6 was
achieved by inducing apoptosis.
稳定微管结构，诱导肿瘤细胞凋亡。本文应用形态学观察，MTT分析法，
DNA梯状电泳，流式细胞术检测术，研究了紫杉醇对成骨肉瘤细胞系
SOSP-9607的细胞毒效应。结果发现，紫杉醇对SOSP-9607的细胞毒作用
主要是通过诱导凋亡实现的。并且证实紫杉醇在体外对成骨肉瘤细胞株
SOSP-9607有较强的杀伤作用。
哺乳动物体内发现了多种半胱氨酸蛋白酶，这些结构特点相似的酶构成
了一个蛋白酶家族，称之为Caspase家族。它在细胞凋亡过程中起着重要作
用，根据Caspase在级联反应中的作用和活化的先后，Caspase的14个成员分
为启动性和效应性Caspase。启动性Caspase在细胞凋亡信号和调节因子的作
用下首先活化，再激活效应性Caspase、活化的效应性Caspase作用于相应的
箩四军医大学博士学位论文
底物导致凋亡。Caspase－6是一种效应Caspase分子，研究表明o甲ase的表
达水平与肿瘤组织细胞凋亡有关。
本实验应用 RT—PCR方法检测了成骨肉瘤细胞株 SOSP—9607 中
Caspase－6的表达，发现其无表达。构建T Caspase七转基固腺病毒叫6载
体，月质体法转染 SOSP—9607，RT—PCR法证实转染后 SOSP—9607 中
Caspase表达明显。进一步通过MTT法W实转染Ca叩ase－6对SOSP－9607
的生长有抑制作用，通过形态学观察及DNA电泳证实这种作用主要是通过
促进细胞凋亡而实现的。
Paclitaxel is new broad-spectrum anti-tumor drug, which has a unique
mechanism of promoting the stability of microtube and inducing apoptosis. In the
present study, the cytotoxic effect of paclitaxel on human osteosarcoma cell line
SOSP-9607 was examined by MTT assay, morphological observation, gel
electrophoresis of DNA, and cell morphology. The results showed that the
cytotoxic effect of paclitaxel on SOSP-9607 cell is achieved by inducing
apoptosis. Also, the killing effect of paclitaxel toward SOSP-9607 cell line was
conffrmed in vitro.
A group of caspase (cycteinyl asparate-specifi protease) was found in mammal.
With similar structure, they constitute a proteases family and play a very
important role in the process of cell apoptosis. Fourteen members of this family
4
could be classified into two groups: initiators and effectors. Caspases exist in an
inactive form in normal cells. When apoptotic signal has been sent in, they will
be cleaved and activated. After initiators have been activated, effectors can be
activated. Active effectors cleave their substrates after an aspartate residue and
induce apoptosis. Caspase-6 is kind of effectors.
The relationship between the expression level of caspase and the apoptosis
of tumor cell was confirmed by many reports.
In this study, we examined the expression of caspase-6 in the osteosarcoma
line SOSP-9067 by RT-PCR method. Results showed no expression of caspase-6.
We constructed a caspase 6 gene-transfer virus adv5 vectors and transfeced it into
the osteosarcoma line SOSP-9607 by way of lipofection. A high expression of
caspase 6 was identified by RT-PCR after the transfection. The cell survival rate
was assayed by MTT method. The result indicates the caspase 6 may inhibit the
growth of the transfected cell. The morphological observation and gel
electrophoresis of DNA also confirmed the inhibition effect of caspase 6 was
achieved by inducing apoptosis.
引文
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