Sun Jun-zhong, Song Hai-feng, Li Liu-shu, Song San-tai, Zhu Jian-hua, Zhao Hui
No. 304 Clinical Department, General Hospital of Chinese People's Liberation Army, Beijing 100039, China.
Zhonghua Yi Xue Za Zhi. 2006 Feb 28;86(8):540-3.
To investigate the inhibitory effect of antisense oligodeoxynucleotides targeting HER-2 mRNA on growth of breast cancer.
Human breast cancer cells of the line SK-BR-3 that overexpresses HER-2 were injected subcutaneously into BALB/c nude mice. Seven to ten days after tumors were collected and made into homogenate. Antisense oligodeoxynucleotide HA6722 targeting HER-2 mRNA and its control sequence Scramble were synthesized. Forty-nine BALB/c nude mice were injected with homogenate of SK-BR-3 cells and then randomly divided into 7 equal groups: Group 1, injected intravenously with docetaxel (TXT) 7.5 mg.kg(-1).d(-1) once a week twice; Group 2, injected intravenously with TXT 15 mg.kg(-1).d(-1) once a week twice; Group 3, injected intravenously with TXT 7.5 mg.kg(-1).d(-1) once a week twice + HA6722 5 mg.kg(-1).d(-1) for 12 days; Group 4, injected intravenously with HA6722 5 mg.kg(-1).d(-1) for 12 days; Group 5, injected intravenously with TXT 7.5 mg.kg(-1).d(-1) once a week twice + Scramble6722 5 mg.kg(-1).d(-1) for 12 days; and Group 7, injected with normal saline. After the drug administration the mice were observed for additional 3-4 weeks to measure the size of tumor every other day. Then the mice were killed and the tumors were taken out to be examined. The inhibition rate was calculated.
The inhibition rate of tumor in Group 3 was 88.3%, not significantly different from that in Group 2 (88.7%, P > 0.05). The inhibition rate in Group 4 was 76.3%. The inhibition rates of tumor of Groups 2, 3, and 4 were all significantly higher than that in Group 7. However, the inhibition rate of tumor of Group 6 was not significantly different from that in Group 7.
Antisense oligodeoxynucleotides targeting HER-2 mRNA inhibits the growth of breast cancer in a sequence specific and dose-dependent manner.
探讨靶向HER-2 mRNA的反义寡脱氧核苷酸对乳腺癌生长的抑制作用。
将过表达HER-2的人乳腺癌SK-BR-3细胞系皮下接种于BALB/c裸鼠。肿瘤形成7至10天后收集并制成匀浆。合成靶向HER-2 mRNA的反义寡脱氧核苷酸HA6722及其对照序列Scramble。49只BALB/c裸鼠接种SK-BR-3细胞匀浆后随机分为7组，每组7只：第1组，静脉注射多西他赛（TXT）7.5 mg·kg-1·d-1，每周1次，共2次；第2组，静脉注射TXT 15 mg·kg-1·d-1，每周1次，共2次；第3组，静脉注射TXT 7.5 mg·kg-1·d-1，每周1次，共2次+HA6722 5 mg·kg-1·d-1，连续12天；第4组，静脉注射HA6722 5 mg·kg-1·d-1，连续12天；第5组，静脉注射TXT 7.5 mg·kg-1·d-1，每周1次，共2次+Scramble6722 5 mg·kg-1·d-1，连续12天；第6组，静脉注射Scramble6722 5 mg·kg-1·d-1，连续12天；第7组，注射生理盐水。给药后继续观察3至4周，隔天测量肿瘤大小。然后处死小鼠，取出肿瘤进行检测，计算抑瘤率。
第3组抑瘤率为88.3%，与第2组（88.7%）差异无统计学意义（P>0.05）。第4组抑瘤率为76.3%。第2、3、4组的抑瘤率均显著高于第7组。然而，第6组的抑瘤率与第7组差异无统计学意义。
靶向HER-2 mRNA的反义寡脱氧核苷酸可通过序列特异性和剂量依赖性方式抑制乳腺癌生长。
