CAJ | 학술논문

目的：探讨索拉非尼、奥沙利铂单药和两药联合应用对人肝癌细胞株HepG2增殖、迁移和侵袭的影响。方法选择人肝癌细胞株HepG2并分为6组处理：奥沙利铂（0?5μg／ml）组（ O）、索拉非尼（2?0μmol／L）组（ S）、同时联合用药（奥沙利铂0?5μg／ml，索拉非尼2?0μmol／L）组（ O＋S）、奥沙利铂（0?5μg／ml）序贯索拉非尼（2?0μmol／L）组（ OS）、索拉非尼（2?0μmol／L）序贯奥沙利铂（0?5μg／ml）组（SO）和加入100μl普通培养液的阴性对照组（C）；分别采用MTT法、流式细胞术、免疫荧光技术、迁移与侵袭实验，观察奥沙利铂、索拉非尼单药和两药联合应用对HepG2细胞增殖、侵袭与转移的作用。结果 MTT法显示，48 h后用药组对HepG2细胞增殖均有显著的抑制作用，O＋S组的细胞抑制率最高，为（72?13±0?99）％，均明显高于O组、S组和SO组（ P＜0?01），但与OS组的差异无统计学意义（ P＞0?05）；流式细胞术及荧光显微镜观察显示，O＋S组处理HepG2细胞48 h的凋亡率最高，达65?33％，但与OS组的差异无统计学意义（ P＞0?05）；细胞迁移实验表明，O＋S组的细胞迁移抑制率为（71?67±6?66）％，均明显高于O组、S组和SO组（P＜0?01），但与OS组的差异无统计学意义（P＞0?05）；O＋S组和OS组均表现为两药协同作用（ P＜0?01），SO组则表现为两药相加作用（ P＜0?05）。细胞侵袭实验表明，O＋S组的细胞侵袭抑制率为（76?00±5?57）％，明显高于O组、S组（P＜0?01）；O＋S组与OS组均表现为两药协同作用。结论同时联用奥沙利铂和索拉非尼或序贯应用两药较其各自单药对人肝癌HepG2细胞的增殖、迁移、侵袭抑制作用更强，其中先用奥沙利铂序贯索拉非尼与同时联用奥沙利铂和索拉非尼的协同增效作用相似，均优于先用索拉非尼序贯奥沙利铂。
목적：탐토색랍비니、오사리박단약화량약연합응용대인간암세포주HepG2증식、천이화침습적영향。방법선택인간암세포주HepG2병분위6조처리：오사리박（0?5μg／ml）조（ O）、색랍비니（2?0μmol／L）조（ S）、동시연합용약（오사리박0?5μg／ml，색랍비니2?0μmol／L）조（ O＋S）、오사리박（0?5μg／ml）서관색랍비니（2?0μmol／L）조（ OS）、색랍비니（2?0μmol／L）서관오사리박（0?5μg／ml）조（SO）화가입100μl보통배양액적음성대조조（C）；분별채용MTT법、류식세포술、면역형광기술、천이여침습실험，관찰오사리박、색랍비니단약화량약연합응용대HepG2세포증식、침습여전이적작용。결과 MTT법현시，48 h후용약조대HepG2세포증식균유현저적억제작용，O＋S조적세포억제솔최고，위（72?13±0?99）％，균명현고우O조、S조화SO조（ P＜0?01），단여OS조적차이무통계학의의（ P＞0?05）；류식세포술급형광현미경관찰현시，O＋S조처리HepG2세포48 h적조망솔최고，체65?33％，단여OS조적차이무통계학의의（ P＞0?05）；세포천이실험표명，O＋S조적세포천이억제솔위（71?67±6?66）％，균명현고우O조、S조화SO조（P＜0?01），단여OS조적차이무통계학의의（P＞0?05）；O＋S조화OS조균표현위량약협동작용（ P＜0?01），SO조칙표현위량약상가작용（ P＜0?05）。세포침습실험표명，O＋S조적세포침습억제솔위（76?00±5?57）％，명현고우O조、S조（P＜0?01）；O＋S조여OS조균표현위량약협동작용。결론동시련용오사리박화색랍비니혹서관응용량약교기각자단약대인간암HepG2세포적증식、천이、침습억제작용경강，기중선용오사리박서관색랍비니여동시련용오사리박화색랍비니적협동증효작용상사，균우우선용색랍비니서관오사리박。
Objective To observe the effect of sorafenib, oxaliplatin alone or in different combination on the proliferation, migration and invasion of human hepatic carcinoma cell line HepG2. Methods Human hepatic carcinoma cell line HepG2 was chosen and divided into 6 groups:oxaliplatin group ( 0?5μg/ml, O) , sorafenib group ( 2?0μmol/L, S) , combination group( oxaliplatin 0?5μg/ml, sorafenib 2?0 μmol/L;O+S) , oxaliplatin sequent by sorafenib group ( oxaliplatin 0?5μg/ml, sorafenib 2?0μmol/L;OS) , sorafenib sequent by oxaliplatin group (sorafenib 2?0 μmol/L, oxaliplatin 0?5 μg/ml; SO), and the negative control group(100 μl common culture, C) . MTT method, immunofluorescence technique, flow cytometry, migration experiment, and invade experiment were used to observe sorafenib, oxaliplatin alone or in different combination on the proliferation, invasion and metastasis of HepG2 cells. Re?sults The results determined by MTT method showed that the treatment groups significantly inhibited the proliferation of HepG2 cells after 48 h. Cell inhibition rate of O+S group was (72?13±0?99)%, which was significantly higher than that of O, S groups and SO group ( P<0?01) , except OS group. Flow cytometry and fluorescence microscopy analysis showed that the apoptosis rate of HepG2 cells in O+S group was the highest ( 65?33%) at 48 h, but it had no significant difference compared with OS group ( P>0?05) . Cell migra?tion experiment showed that the inhibition rate of cell migration in O+S group was (71?67±6?66)%, which was significantly higher than that of O, S groups and SO group( P<0?01) , except OS group. O+S group and OS group exhibited synergistic effect of both sor?afenib and oxaliplatin ( P<0?01) , while SO group showed additive effect ( P<0?05) . Cells invade experiment showed that cell invasion inhibition rate of O+S group was (76?00±5?57)%, which was significantly higher than that of O, and S groups(P<0?01). There were two drugs synergistic effect in O+S group and OS group. Conclusion Compared with single drug of sorafenib or oxaliplatin, the inhibi?tion of proliferation, migration and invasion of HepG2 cells treated by combination and sequential application of sorafenib, oxaliplatin are higher. The synergistic effect is similar between oxaliplatin sequent by sorafenib and sorafenib in combination with oxaliplatin, which are better than sorafenib sequent by oxaliplatin.