[논문]난소암에서 봉독이 세포자멸사와 JAK2/STAT3 Pathway의 억제에 미치는 영향

안병준; 송호섭

[국내논문] 난소암에서 봉독이 세포자멸사와 JAK2/STAT3 Pathway의 억제에 미치는 영향
Effect of Bee Venom Death Receptor Dependent Apoptosis and JAK2/STAT3 Pathway in the Ovarian Cancer 원문보기

大韓鍼灸學會誌= The journal of Korean Acupuncture & Moxibustion Society, v.29 no.1, 2012년, pp.47 - 59

안병준 (경원대학교 한의과대학 침구학교실) , 송호섭 (경원대학교 한의과대학 침구학교실)

초록
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목적 : 이 연구는 봉독이 사람의 난소암 세포인 SKOV3와 PA-1에서 death receptor의 발현을 높여 세포자멸사를 촉진함으로써 암세포의 성장을 억제하는지 밝히고자 하였다. 방법 : 난소암의 세포자멸사의 관찰에는 DAPI, TUNEL staining assay를 시행하였으며, 세포자멸사 조절 단백질의 변동 관찰에는 western blot analysis를 시행하였고, 난소암 세포에서 death receptor의 변화를 관찰하기 위해 RT-PCR analysis를 시행하였다. 결과 : 1. DAPI, TUNEL staining assay 결과, 봉독은 투여량에 따라 세포자멸사의 유도를 통해 SKOV3와 PA-1 난소암세포의 증식을 억제하였고, 세포자멸사와 동반하여 DR4와 DR6의 발현이 두 암세포 모두에서 증가하였고, DR3의 출현은 PA-1 세포에서 증가하였다. 2. Death Receptor의 발현 증가에 따라 caspase-3, 8, 9 and Bax를 포함하는 세포자멸사 촉진 단백질의 발현이 동반하여 상승하였고 JAK2, STAT3의 인산화와 Bcl-2의 발현은 억제되었다. 3. siRNA 처리 시 봉독에 의한 DR3, DR4, DR6 발현증가와 STAT3의 활성억제가 역전되었다. 결론 : 이러한 결과는 봉독이 난소암 세포에서 DR3, DR4, DR6의 증가와 JAK2/STAT3 pathway의 억제를 통하여 세포자멸사를 유발한다는 것을 시사하며, 난소암의 예방과 치료에 효과적으로 활용될 수 있을 것으로 기대된다.

주제어

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제안 방법

Cells were treated with bee venom(1, 2, and 5 ㎍/ml) for 24 hr, and total RNA were extracted and examined for expressions of TNF-R1, TNF-R2, FAS, DR-3, -4, -5, -6, and GAPDH by RT-PCR. GAPDH was used as an internal control to show equal RNA loading.
To determine the inhibition of cell growth by bee venom was due to the induction of apoptotic cell death, we evaluated the changes in the chromatin morphology of cells by using DAPI staining followed by TUNEL staining assays, and then the double labeled cells were analyzed by fluorescence microscope. Conversely well with cell growth inhibition, DAPI-stained TUNEL-positive cells were significantly increased in bee venom treated cells.
Similarly, my data demonstrated that bee venom increased expression of pro-apoptotic proteins, Bax, cleaved form of caspase-3, -8, and -9 and decreased expression of anti-apoptotic protein, Bcl-2. To further investigate the involvement of death receptors in bee venom-induced apoptotic cell death, I used siRNA of DR3, DR4, and DR6, and found that bee venom-induced apoptotic cell death of ovarian cancer cells was reversed by these receptor siRNA and it was abolished in PA-1 cells by DR4 knock down. Consistent with the previous Yang et al.

대상 데이터

The SKOV3 and PA-1 ovarian cancer cell lines were purchased from the American Type Culture Collection (Manassas, VA). SKOV3 cancer cells were cultured in RPMI-1640 medium supplemented with 10% fetal bovine serum (FBS) and penicillin/streptomycin (100 U/ml).

데이터처리

Data are presented as mean±SD. The differences in all data were assessed by one-way analysis of variance (ANOVA). When the P value in the ANOVA test indicated statistical significance, the differences were assessed by the Dunnett’s test.
When the P value in the ANOVA test indicated statistical significance, the differences were assessed by the Dunnett’s test.

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