구강편평상피세포암종에서 CGM과 독소루비신 병용 처리에 의한 세포자멸사 유도와 전이억제 효과
Combination treatment with Chios gum mastic and doxorubisin in OSCC: Induction of apoptosis and inhibition of metastasis
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초록
구강암은 두경부 영역에 발생하는 악성종양으로 국소적 침윤과 경부 림프절 전이가 빈번하여 사망률이높고 전 세계적으로 발생 빈도가 증가하고 있는 추세이다. 외과적 수술, 방사선요법, 항암제를 통한 다각적인 치료에도 불구하고 환자의 5년 생존율이 약 50% 정도밖에 되지 않으며 치료에 사용되는 항암제는 다양한 부작용을 동반하는 경우가 많으므로 기존 약물의 부작용을 최소화 하면서 동등한 효력을 가지는 항암제의 개발이 요구되는 실정이다. 본 연구에서는 Pistacia lenticulus 나무의 잎과 줄기에서 추출한 천연 추출물인 CGM과 기존 항암제인 독소루비신을 병용 처리하여 세포자멸사를 유도하였으며 암세포의 이동력과 침습력을 억제 시켰다. 또한 암의 전이에 관여하는 EMT 관련 단백질의 발현을 확인하였다. 그 결과 세포자멸사의 내인성 경로를 통하여 세포사멸사가 유도되었으며, EMT관련 단백질인 E-cadherin의 발현이 증가하였으며 N-cadherin, snail. slug의 발현이 억제되는 것을 확인할 수 있었다. 따라서 본 연구에서는 CGM과독소루비신의 병용 처리를 통하여 CGM단독처리보다 낮은 농도로 효과적인 항암 활성 효과를 유도하였으며, CGM이 구강암의 치료제로서 효용가능성이 있음을 밝혔다.
Abstract
Oral squamous cell carcinoma (OSCC) is currently the most malignant cancer of the head and neck, affecting tens of thousands of patients per year worldwide. The natural compound CGM from Pistacia lentiscus var Chia has been known for its aromatic and therapeutic characteristics for thousands of years. CGM has antimicrobial, antifungal, antioxidant, anti-inflammatory, and anticancer properties. We confirmed that co-treatment with CGM and doxorubicin effectively decreased proliferation and viability in human OSCC cells. In addition, OSCC cell migration, invasion, and EMT were inhibited by co-treatment with CGM and doxorubicin. Taken together, our findings suggested that CGM and doxorubicin induced apoptosis via the activation of intrinsic pathways and inhibits cell invasion and migration by inhibiting the EMT-inducing transcription factors. These findings suggest that co-treatment with CGM and doxorubicin may potentially contribute to oral cancer treatment and provide useful information for the development of a new therapeutic agent.
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