癌变·畸变·突变
癌變·畸變·突變
암변·기변·돌변
CARCINOGENSES,TERATOGENSIS AND MUTAGENESIS
2013年
4期
267-271
,共5页
李哲萍%刘小丽%武希润%申慧琴%康贵云%王琦
李哲萍%劉小麗%武希潤%申慧琴%康貴雲%王琦
리철평%류소려%무희윤%신혜금%강귀운%왕기
FOLFOX4%1-甲基-色氨酸%吲哚胺-2,3-双加氧酶%胃癌
FOLFOX4%1-甲基-色氨痠%吲哚胺-2,3-雙加氧酶%胃癌
FOLFOX4%1-갑기-색안산%신타알-2,3-쌍가양매%위암
FOLFOX4%1-methyl tryptophan%indoleamine-2,3-dioxygenase%gastric cancer
目的：观察FOLFOX4联合1-甲基-色氨酸(1-methyl tryptophan，1-MT)对荷胃癌小鼠皮下移植瘤生长的抑制作用，以及对胃癌组织吲哚胺-2，3-双加氧酶(indoleamine-2，3-dioxygenase，IDO)表达的影响。方法：将IDO真核表达质粒(pcDNA3.1-IDO)转染小鼠胃癌细胞MFC，建立稳定表达IDO的细胞株，RT-PCR与Western blot法检测细胞中IDO的表达。小鼠皮下接种转染pcDNA3.1-IDO的MFC细胞悬液，建立高表达IDO的小鼠胃癌皮下移植瘤模型(32只)，同时设空白对照(8只，接种未转染的MFC细胞)和阴性对照(8只，接种转染pcDNA3.1质粒的MFC细胞)，观察各组小鼠成瘤情况。将32只模型小鼠随机分为1-MT治疗组、FOLFOX4治疗组、FOLFOX4+1-MT联合治疗组和未治疗组(阳性对照组)，每组8只。治疗组分别注射给予1-MT、FOLFOX4或FOLFOX4+1-MT，阳性对照组给予生理盐水。观察各组小鼠一般情况及肿瘤质量差异。注射细胞悬液后第12天处死所有小鼠，剥离瘤体并称重，计算各组小鼠平均瘤质量及抑瘤率，另取肿瘤标本采用免疫组织化学染色法检测胃癌组织中IDO的表达。结果：RT-PCR与Western blot均检测到pcDNA3.1-IDO转染细胞中IDO的表达。高表达IDO的胃癌皮下移植瘤模型小鼠肿瘤质量大于空白对照组和阴性对照组小鼠(P<0.05)，且其胃癌组织IDO的表达亦较空白对照组和阴性对照组明显增加(P<0.05)。给予1-MT、FOLFOX4和FOLFOX4+1-MT治疗后，模型小鼠进食量均不同程度增加，行动较之前灵活，嗜睡也有不同程度好转，FOLFOX4+1-MT联合治疗组小鼠症状基本缓解。1-MT治疗组、FOLFOX4治疗组和FOLFOX4+1-MT联合治疗组小鼠肿瘤质量均小于未治疗组(P<0.05)，其抑瘤率分别为8.91%、80.20%、86.13%，FOLFOX4+1-MT联合治疗组小鼠肿瘤质量小于1-MT治疗组和FOLFOX4治疗组(P<0.05)。1-MT治疗组、FOLFOX4治疗组和FOLFOX+1-MT联合治疗组小鼠胃癌组织中IDO的表达均低于未治疗组(P<0.05)；FOLFOX4+1-MT联合治疗组胃癌组织中IDO的表达低于1-MT治疗组和FOLFOX4治疗组(P<0.05)。结论：1-MT对胃癌小鼠皮下移植瘤的生长和胃癌组织IDO的表达具有抑制作用，并能与FOLFOX4发挥协同抗肿瘤作用。
目的：觀察FOLFOX4聯閤1-甲基-色氨痠(1-methyl tryptophan，1-MT)對荷胃癌小鼠皮下移植瘤生長的抑製作用，以及對胃癌組織吲哚胺-2，3-雙加氧酶(indoleamine-2，3-dioxygenase，IDO)錶達的影響。方法：將IDO真覈錶達質粒(pcDNA3.1-IDO)轉染小鼠胃癌細胞MFC，建立穩定錶達IDO的細胞株，RT-PCR與Western blot法檢測細胞中IDO的錶達。小鼠皮下接種轉染pcDNA3.1-IDO的MFC細胞懸液，建立高錶達IDO的小鼠胃癌皮下移植瘤模型(32隻)，同時設空白對照(8隻，接種未轉染的MFC細胞)和陰性對照(8隻，接種轉染pcDNA3.1質粒的MFC細胞)，觀察各組小鼠成瘤情況。將32隻模型小鼠隨機分為1-MT治療組、FOLFOX4治療組、FOLFOX4+1-MT聯閤治療組和未治療組(暘性對照組)，每組8隻。治療組分彆註射給予1-MT、FOLFOX4或FOLFOX4+1-MT，暘性對照組給予生理鹽水。觀察各組小鼠一般情況及腫瘤質量差異。註射細胞懸液後第12天處死所有小鼠，剝離瘤體併稱重，計算各組小鼠平均瘤質量及抑瘤率，另取腫瘤標本採用免疫組織化學染色法檢測胃癌組織中IDO的錶達。結果：RT-PCR與Western blot均檢測到pcDNA3.1-IDO轉染細胞中IDO的錶達。高錶達IDO的胃癌皮下移植瘤模型小鼠腫瘤質量大于空白對照組和陰性對照組小鼠(P<0.05)，且其胃癌組織IDO的錶達亦較空白對照組和陰性對照組明顯增加(P<0.05)。給予1-MT、FOLFOX4和FOLFOX4+1-MT治療後，模型小鼠進食量均不同程度增加，行動較之前靈活，嗜睡也有不同程度好轉，FOLFOX4+1-MT聯閤治療組小鼠癥狀基本緩解。1-MT治療組、FOLFOX4治療組和FOLFOX4+1-MT聯閤治療組小鼠腫瘤質量均小于未治療組(P<0.05)，其抑瘤率分彆為8.91%、80.20%、86.13%，FOLFOX4+1-MT聯閤治療組小鼠腫瘤質量小于1-MT治療組和FOLFOX4治療組(P<0.05)。1-MT治療組、FOLFOX4治療組和FOLFOX+1-MT聯閤治療組小鼠胃癌組織中IDO的錶達均低于未治療組(P<0.05)；FOLFOX4+1-MT聯閤治療組胃癌組織中IDO的錶達低于1-MT治療組和FOLFOX4治療組(P<0.05)。結論：1-MT對胃癌小鼠皮下移植瘤的生長和胃癌組織IDO的錶達具有抑製作用，併能與FOLFOX4髮揮協同抗腫瘤作用。
목적：관찰FOLFOX4연합1-갑기-색안산(1-methyl tryptophan，1-MT)대하위암소서피하이식류생장적억제작용，이급대위암조직신타알-2，3-쌍가양매(indoleamine-2，3-dioxygenase，IDO)표체적영향。방법：장IDO진핵표체질립(pcDNA3.1-IDO)전염소서위암세포MFC，건립은정표체IDO적세포주，RT-PCR여Western blot법검측세포중IDO적표체。소서피하접충전염pcDNA3.1-IDO적MFC세포현액，건립고표체IDO적소서위암피하이식류모형(32지)，동시설공백대조(8지，접충미전염적MFC세포)화음성대조(8지，접충전염pcDNA3.1질립적MFC세포)，관찰각조소서성류정황。장32지모형소서수궤분위1-MT치료조、FOLFOX4치료조、FOLFOX4+1-MT연합치료조화미치료조(양성대조조)，매조8지。치료조분별주사급여1-MT、FOLFOX4혹FOLFOX4+1-MT，양성대조조급여생리염수。관찰각조소서일반정황급종류질량차이。주사세포현액후제12천처사소유소서，박리류체병칭중，계산각조소서평균류질량급억류솔，령취종류표본채용면역조직화학염색법검측위암조직중IDO적표체。결과：RT-PCR여Western blot균검측도pcDNA3.1-IDO전염세포중IDO적표체。고표체IDO적위암피하이식류모형소서종류질량대우공백대조조화음성대조조소서(P<0.05)，차기위암조직IDO적표체역교공백대조조화음성대조조명현증가(P<0.05)。급여1-MT、FOLFOX4화FOLFOX4+1-MT치료후，모형소서진식량균불동정도증가，행동교지전령활，기수야유불동정도호전，FOLFOX4+1-MT연합치료조소서증상기본완해。1-MT치료조、FOLFOX4치료조화FOLFOX4+1-MT연합치료조소서종류질량균소우미치료조(P<0.05)，기억류솔분별위8.91%、80.20%、86.13%，FOLFOX4+1-MT연합치료조소서종류질량소우1-MT치료조화FOLFOX4치료조(P<0.05)。1-MT치료조、FOLFOX4치료조화FOLFOX+1-MT연합치료조소서위암조직중IDO적표체균저우미치료조(P<0.05)；FOLFOX4+1-MT연합치료조위암조직중IDO적표체저우1-MT치료조화FOLFOX4치료조(P<0.05)。결론：1-MT대위암소서피하이식류적생장화위암조직IDO적표체구유억제작용，병능여FOLFOX4발휘협동항종류작용。
OBJECTIVE:To observe the inhibitory effect of FOLFOX4 combined with 1-MT on subcutaneous xenografts of gastric cancer in mice,and its influence on the expression of indoleamine-2,3-dioxygenase (IDO) in gastric cancer tissue. METHODS:Transfect the IDO eukaryotic expression plasmids (pcDNA3.1-IDO) into mice gastric cancer cell line MFC. The cell line expressing IDO stably was established. Expression of IDO was detected by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. Suspension of the MFC cells transfected with pcDNA3.1-IDO plasmid were inoculated subcutaneously in mice. Mice gastric carcinoma subcutaneous xenografts model expressing IDO highly was established (n=32). Blank control (n=8,untransfected MFC cells) and negative control (n=8,transfected MFC cells) were set up. The 32 model mice were randomly divided into 1-MT treatment group, FOLFOX4 treatment group, FOLFOX4+1-MT combined treatment(saline) group and non-treatment group (positive control group). There were eight mice in each group. The general condition of the mice and the differences in tumor quality were observed. Twelve day after cell suspension injection,all of the mice were sacrificed. The tumors were excised and weighed. Average tumor size and the tumor inhibitory rates of each group were calculated. The expression of IDO in gastric carcinoma tissues was evaluated by immunohistochemistry. RESULTS:Tumor of mice gastric carcinoma subcutaneous xenografts model expressing IDO highly was greater than blank control and negative control groups (P<0.05) and the expression of IDO in gastric carcinoma tissue was also increased significantly(P<0.05). After given 1-MT,FOLFOX4 and FOLFOX4+1-MT treatments,the food intake of model mice increased to varying degrees,more agile than before,and lethargy was also improved to different extents. The symptoms of FOLFOX4+1-MT combined treatment group were basically resolved. The tumors of 1-MT treatment,FOLFOX4 treatment and FOLFOX4+1-MT combined treatment group were smaller than no treatment group (P<0.05). The tumour inhibitory rates were 8.91%,80.20%,86.13%,respectively. FOLFOX4+1-MT combined treatment group tumor was less than 1-MT treatment group and FOLFOX4 treatment groups (P<0.05). The expressions of IDO in gastric carcinoma tissue of 1-MT treatment,FOLFOX4 treatment and FOLFOX+1-MT combined groups were lower than non-treatment group (P<0.05). The expression of IDO in gastric cancer tissue of FOLFOX4+1-MT combined treatment group was lower than 1-MT treatment group and FOLFOX4 treatment groups (P<0.05). CONCLUSION:1-MT could inhibit the growth of subcutaneous xenografts of gastric carcinoma and the expression of IDO in gastric carcinoma tissue in mice. It could play synergistic antitumor role together with FOLFOX4.
