[Inhibition effect of liposomes survivin antisense oligonucleotide on human gastric carcinoma transplanted subcutaneously in nude mice]

Zhonghua Wai Ke Za Zhi. 2004 Nov 22;42(22):1367-71.
[Article in Chinese]

Abstract

Objective: To study the inhibitory effect and reasons of liposomes survivin antisense oligonucleotides (ASODN) on growth of human gastric carcinoma transplanted subcutaneously in nude mice.

Methods: Human gastric carcinoma transplanted subcutaneously in nude mice model was established, and subsequently was divided randomly into six groups: control group, liposome group, sense oligonucleotide (SODN) group, 100, 200 and 400 nmol/L ASODN group. Different treatments were given respectively. The weight and volume of subcutaneous tumors were measured, and tumor growth inhibitory rate and decreased rate was calculated. The morphological changes of transplanted tumor cells were observed under light microscope. The expression of survivin was detected by immunohistology (SP). Changes of survivin gene transcription and protein expression were determined by western blot and RT-PCR.

Results: Growth of the tumors was significantly inhibited in all ASODN groups as compared with that in the control, liposome and SODN group. The highest growth inhibitory rate in the 400 nmol/L group is 93%. The number of apoptotic cells of ASODN group increased and expression of survivin became weaken under the microscope. Liquified necrosis regions could be seen in 6 cases (6/12) of tumor tissues. The content of survivin mRNA and protein decreased in all survivin ASODN groups. The survivin protein expression of 400 nmol/L group was about 36.8% of the control group.

Conclusions: Survivin gene ASODN can inhibit the growth of human gastric carcinoma in nude mice by inducing cells apoptosis and decreasing the expression of survivin mRNA and protein.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects*
  • Humans
  • Inhibitor of Apoptosis Proteins
  • Liposomes
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Microtubule-Associated Proteins / biosynthesis
  • Microtubule-Associated Proteins / genetics*
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics*
  • Neoplasm Transplantation
  • Oligonucleotides, Antisense / genetics
  • Oligonucleotides, Antisense / pharmacology*
  • RNA, Messenger / genetics
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / therapy*
  • Survivin

Substances

  • Antineoplastic Agents
  • BIRC5 protein, human
  • Inhibitor of Apoptosis Proteins
  • Liposomes
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • Oligonucleotides, Antisense
  • RNA, Messenger
  • Survivin