Related Experiment Video
Updated: Aug 8, 2026
Live Cell Imaging of the TGF- β/Smad3 Signaling Pathway In Vitro and In Vivo Using an Adenovirus Reporter System
Published on: July 30, 2018
[Development of a novel gene therapy using survivin antisense expressing adenoviral vectors]
Tetsuhisa Yamamoto1, Yoshinobu Manome, Akiko Miyamoto
1Dept. of General and Gastroenterological Surgery, Osaka Medical College.
Background:
Survivin, a novel inhibitor of apoptosis, is undetectable in normal adult tissues but becomes notably expressed in the most common human cancers, and is recognized as a potential target in anticancer therapy.
Methods:
In this study we evaluated a survivin antisense expressing replication-incompetent adenoviral vector under the control of the cytomegalovirus promoter (pAd.CMV-SAS) for cytoreductive effects in human HT-29 colon cancer cells in vitro and in vivo.
Results:
Infection of tumor cells with pAd.CMV-SAS caused down-regulation of survivin expression and the potential for spontaneous apoptosis in tumor cells. In contrast, pAd.CMV-SAS did not affect cell viability of normal human cells including fibroblasts. In addition, infection of tumor cells with pAd.CMV-SAS resulted in an increase of the G0/G1 phase population in the cell cycle, and increased their sensitivity to chemotherapeutic drugs in vitro. The efficacies of pAd.CMV-SAS were inversely correlated with survivin expression level. In nude mice, pAd.CMV-SAS suppressed tumor formation, as well as decreased the tumor volumes to approximately 30% of the control tumors. Furthermore, it was confirmed that the anti-tumor efficacy of pAd.CMV-SAS was also enhanced in combination with chemotherapeutic drugs in vivo.
Conclusions:
These findings suggest that targeting of survivin using adenoviral antisense vectors may have a potential role in the selective therapy of colon cancer.
Insights
This study shows that an adenoviral vector targeting survivin (pAd.CMV-SAS) effectively reduces colon cancer cell growth and tumor volume in vivo. The treatment selectively targets cancer cells, sparing normal cells and enhancing chemotherapy efficacy.
Area of Science:
- Oncology
- Molecular Biology
- Gene Therapy
Background:
- Survivin is a key inhibitor of apoptosis, highly expressed in many human cancers but not normal adult tissues.
- Its expression in cancer makes survivin a promising target for novel anticancer therapies.
Purpose of the Study:
- To evaluate the cytoreductive potential of a survivin antisense adenoviral vector (pAd.CMV-SAS) against human colon cancer cells.
- To assess the in vitro and in vivo efficacy and selectivity of pAd.CMV-SAS.
Main Methods:
- Human HT-29 colon cancer cells and normal fibroblasts were infected with pAd.CMV-SAS.
- In vitro and in vivo experiments were conducted in cell cultures and nude mouse models.
- Cell viability, apoptosis, cell cycle, and tumor growth were analyzed.
Main Results:
- pAd.CMV-SAS effectively downregulated survivin expression, inducing apoptosis in colon cancer cells but not normal cells.
- The vector increased the G0/G1 phase population and enhanced sensitivity to chemotherapy in vitro.
- In vivo, pAd.CMV-SAS suppressed tumor formation and reduced tumor volume by approximately 70%, with enhanced efficacy when combined with chemotherapy.
Conclusions:
- Adenoviral antisense targeting of survivin demonstrates significant potential for selective colon cancer therapy.
- pAd.CMV-SAS offers a promising strategy for cancer treatment, particularly in combination with existing chemotherapeutic drugs.
