한국인 유래 구강암 세포주 YD-38에서 metformin에 의한 세포성장 억제

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Metformin, Cell death, Apoptosis, Anti-cancer therapy, Oral cancer cells
Metformin (1,1-dimethylbiguanide hydrochloride), derived from French lilac (Galega officinalis), is a first-line drug prescribed for patients with type 2 diabetes. It has been reported to have anti-cancer effects in the variety of cancer cells. However, metformin effects on oral cancer cells are not clearly established. The main goal of this study was to investigate the effect of metformin on cell growth and apoptosis induction in oral cancer cells derived from Korean.
To determine the effect of metformin on cell growth and apoptosis induction in oral cancer cells, it was examined by inhibition of cell growth (MTT assay), DNA fragmentation analysis and immunoblotting in YD-38 human oral cancer cells derived from Korean. The results are as follows.

1. Treatment of metformin induced the inhibition of cell growth depended on the metformin treatment time and concentration in YD-38 cells.
2. Treatment of metformin induced the nuclear fragmentation in YD-38 cells.
3. Metformin promoted proteolytic cleavages of procaspase-3 with the increases in the amount of cleaved caspase-3.
4. Cleaved PARP was increased by metformin in YD-38 cells.
5. Treatment of YD-38 cells with metformin increased the level of Bax but decreased the level of Bcl-2.

These results suggest that the metformin can induce the suppression of cell growth and cell apoptosis in YD-38 human oral cancer cells derived from Korean through both the death receptor-mediated extrinsic apoptotic pathway and the mitochondria-mediated intrinsic apoptotic pathway, and that it may have potential properties for anti-cancer drug discovery.| French lilac(Galega officinalis)에서 유래한 metformin(1,1-dimethylbiguanide hydrochloride)은 type 2 당뇨병 치료제 이며, 최근 들어 특정 암세포의 성장을 억제할 수 있다고 보고되었다. 그러나 구강암과 관련된 metformin에 관한 자료는 매우 부족하다. 따라서 본 연구에서는 한국인에서 유래한 구강암 세포주 YD-38 세포를 이용하여 metformin의 구강암세포 성장억제에 미치는 효과와 세포성장 억제기전을 분석하였다.
본 연구에서 metformin에 의한 구강암세포 성장억제와 그 기전을 조사하기 위해, YD-38 세포주에서 metformin을 이용하여 MTT 분석, DNA fragmentation 분석 및 immunoblotting 등을 시행하였다.
사람 구강암 세포주 YD-38에서 metformin은 구강암세포의 성장을 시간과 농도에 의존적으로 억제하였다. YD-38 세포에서 metformin은 핵의 파쇄 및 분절을 유도하였다. YD-38 세포에 metformin을 처리한 실험군에서 procaspase-3 및 PARP의 proteolytic cleavage 현상을 확인할 수 있었다. YD-38 세포에 metformin을 처리한 실험군에서 Bax 단백의 발현은 증가하였으나, Bcl-2 단백의 발현은 감소하였다.

본 연구의 결과로 metformin은 한국인 유래 구강암 세포주 YD-38의 apoptosis를 유도하여 구강암세포 성장을 억제시키는 것으로 사료된다. 또한 본 연구의 결과로, metformin을 이용한 구강암세포의 성장억제에 관한 하나의 방향을 제시할 수 있을 것으로 사료된다.
Alternative Title
Growth inhibition by metformin in YD-38 oral cancer cells derived from Korean
Alternative Author(s)
Seo Dong Kuk
일반대학원 치의학과
Awarded Date
Table Of Contents
TABLE OF CONTENT -------------------------------------------- ⅰ
LIST OF TABLE -------------------------------------------------- ⅲ
LIST OF FIGURES ------------------------------------------------ ⅳ

ABSTRACT -------------------------------------------------------- ⅴ

I. INTRODUCTION ------------------------------------------------- 1

II. MATERIALS AND METHODS --------------------------------- 3
1. Materials --------------------------------------------------------- 3
2. Cell line and cell cultures ------------------------------------------ 3
3. Cell viability assay (MTT assay) ----------------------------------- 3
4. DNA fragmentation analysis ----------------------------------------- 4
5. Immunoblotting --------------------------------------------------- 4
6. Data analysis ------------------------------------------------------ 5

Ⅲ. RESULTS ---------------------------------------------------- 6
1. Cytotoxic effect of metformin in YD-38 cells ------------------------- 6
2. DNA fragmentation by metformin in YD-38 cells -------------------- 7
3. Activation of caspase-3 by metformin ------------------------------- 7
4. Apoptosis mediated via PARP by metformin ------------------------- 7
5. Apoptosis-related signal pathways by metformin ------------------ 8

Ⅳ. DISCUSSION ----------------------------------------------- 9

Ⅴ. REFERENCES ----------------------------------------------- 12

Ⅵ. FIGURE LEGENDS ------------------------------------------ 20

Ⅶ. FIGURES ---------------------------------------------------- 22

ABSTRACT in KOREAN ---------------------------------------- 28
서동국. (2016). 한국인 유래 구강암 세포주 YD-38에서 metformin에 의한 세포성장 억제.
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General Graduate School > 4. Theses(Ph.D)
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