Synergistic effects of Akt1 shRNA and paclitaxel-incorporated conjugated linoleic acid-coupled poloxamer thermosensitive hydrogel on breast cancer

Ding-Ding Guo; Seong-Ho Hong; Hu-Lin Jiang; Ji-Hye Kim; Arash Minai-Tehrani; Ji-Eun Kim; Ji-Young Shin; Tao Jiang; You-Kyoung Kim; Yun-Jaie Choi; Chong-Su Cho; Myung-Haing Cho

doi:10.1016/j.biomaterials.2011.12.011

Synergistic effects of Akt1 shRNA and paclitaxel-incorporated conjugated linoleic acid-coupled poloxamer thermosensitive hydrogel on breast cancer

Biomaterials. 2012 Mar;33(7):2272-81. doi: 10.1016/j.biomaterials.2011.12.011. Epub 2011 Dec 16.

Authors

Ding-Ding Guo¹, Seong-Ho Hong, Hu-Lin Jiang, Ji-Hye Kim, Arash Minai-Tehrani, Ji-Eun Kim, Ji-Young Shin, Tao Jiang, You-Kyoung Kim, Yun-Jaie Choi, Chong-Su Cho, Myung-Haing Cho

Affiliation

¹ Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151 921, Republic of Korea.

PMID: 22177840
DOI: 10.1016/j.biomaterials.2011.12.011

Abstract

The phosphoinositide 3-kinase/Akt1 signaling pathway has emerged as a target for cancer therapy. In this study, we aimed to develop a strategy to enhance Akt-targeted cancer therapy. We hypothesized that combination of Akt1-targeted therapy with conventional chemotherapy using paclitaxel-incorporated conjugated linoleic acid-coupled poloxamer thermosensitive hydrogel may have synergistic effects in cancer therapeutic efficiency compared with chemotherapy alone. In this study, we found that the combination of shAkt1 with paclitaxel exerted synergistic anti-cancer effects, thus, inhibiting the growth of human breast cancer cells, and breast cancer xenografts in mice as well. The combination therapy demonstrated enhanced anti-cancer effects through inhibiting Akt1 signaling and inducing apoptosis. Our results suggest that the presented strategy of combination of shAkt1 with paclitaxel may have a potential for treatment of breast cancer.

Publication types

Evaluation Study
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / chemistry
Antineoplastic Agents / metabolism
Antineoplastic Agents / therapeutic use*
Apoptosis / drug effects
Breast Neoplasms / drug therapy*
Cell Line, Tumor / drug effects
Female
Humans
Hydrogel, Polyethylene Glycol Dimethacrylate / chemistry*
Hydrogel, Polyethylene Glycol Dimethacrylate / metabolism
Linoleic Acids, Conjugated / chemistry*
Linoleic Acids, Conjugated / metabolism
Materials Testing
Mice
Mice, Inbred BALB C
Mice, Nude
Neoplasm Transplantation
Paclitaxel / chemistry
Paclitaxel / metabolism
Paclitaxel / pharmacology
Paclitaxel / therapeutic use*
Poloxamer / chemistry*
Poloxamer / metabolism
Proto-Oncogene Proteins c-akt / genetics*
Proto-Oncogene Proteins c-akt / metabolism
RNA, Small Interfering / pharmacology
RNA, Small Interfering / therapeutic use*
Signal Transduction / physiology

Substances

Antineoplastic Agents
Linoleic Acids, Conjugated
RNA, Small Interfering
Poloxamer
Hydrogel, Polyethylene Glycol Dimethacrylate
Proto-Oncogene Proteins c-akt
Paclitaxel