ERK1/2経路を介した大腸癌患者の化学療法に対するPD98059の効果

Effect of PD98059 on chemotherapy in patients with colorectal cancer through ERK1/2 pathway.

• Yinpeng Li
• Qiu Yang

抄録

目的:

MAPK/ERKシグナル伝達経路阻害剤PD98059とパクリタキセルの併用が大腸がん細胞の増殖、浸潤、アポトーシス能に及ぼす影響を調べる。

PURPOSE: To investigate the effects of MAPK/ERK signaling transduction pathway inhibitor PD98059 combined with paclitaxel on the proliferative, invasive and apoptotic abilities of colorectal cancer cells.

方法:

大腸癌（CRC）SW-480細胞を選択し、通過後3群に分けた。ブランク群（無処理）、対照群（PD98059ブロッカー（25μmol/L）で処理）、観察群（PD98059ブロッカー（25μmol/L）とパクリタキセル（100μmol/L）を併用して処理）。

METHODS: Colorectal cancer (CRC) SW-480 cells were selected and divided into 3 groups after passage: Blank group (not treated), control group (treated with PD98059 blocker (25μmol/L)), observation group (treated with PD98059 blocker (25μmol/L) combined with paclitaxel (100μmol/L)).

結果:

各群の細胞の増殖、浸潤およびアポトーシスを登録した。ERK1/2およびp-ERK1/2タンパク質の相対発現をウエスタンブロットで評価した。BaxおよびBcl-2の相対発現はRT-PCRにより評価した。対照群の増殖能は観察群に比べて有意に高かった（p＜0.05）。コントロール群のp-ERK1/2タンパク質の相対発現量は観察群よりも有意に高かった(p<0.05)。ブランク群の浸潤能は他の2群と比較して有意に高く(p<0.05)、対照群の浸潤能は観察群と比較して有意に高かった(p<0.05)。また、対照群のアポトーシス能は観察群に比べて有意に低かった(p<0.05)。また、観察群の細胞におけるBcl-2の発現は、ブランク群と対照群との比較で有意に高く、対照群の発現はブランク群との比較で有意に高かった(p<0.05)。また、観察群の細胞におけるBaxの発現は、ブランク群および対照群に比べて有意に低かった(p<0.05)。

RESULTS: The proliferation, invasion and apoptosis of cells in each group were registered. The relative expressions of ERK1/2 and p-ERK1/2 protein were assessed by Western blot. The relative expressions of Bax and Bcl-2 were assessed by RT-PCR. The proliferation ability in the control group was significantly higher than that in the observation group (p<0.05). The relative expression of p-ERK1/2 protein in the control group was significantly higher than that in the observation group (p<0.05). The invasive ability in the blank group was significantly higher than that in the other two groups (p<0.05), and that in the control group was significantly higher than that in the observation group (p<0.05). The apoptotic ability in the control group was significantly lower than that in the observation group p<0.05). The expression of Bcl-2 in the cells of the observation group was significantly higher than that of the blank group and the control group, and that in the control group was higher than that in the blank group (p<0.05). The expression of Bax in the cells of the observation group was significantly lower than that of the blank group and the control group (p<0.05).

結論:

阻害剤PD98059とパクリタキセルを併用することで、ERK1/2シグナル伝達経路におけるERK1/2の発現に影響を与え、CRC細胞の増殖・浸潤能力を効果的に阻害し、CRC細胞のアポトーシス能力を高めることができ、CRCの臨床治療薬としての可能性が期待される。

CONCLUSIONS: Inhibitor PD98059 combined with paclitaxel can affect the expression of ERK1/2 in ERK1/2 signaling pathway, effectively inhibit the proliferation and invasive abilities of CRC cells, increase the apoptotic ability of CRC cells, and is expected to become a potential drug for clinical treatment of CRC.