Lentivirus-mediated carboxyl-terminal modulator protein gene transfection via aerosol in lungs of K-ras null mice

Abstract

The low efficiency of conventional therapies in achieving long-term survival of lung cancer patients calls for development of novel options. Aerosol gene delivery may provide the alternative for safe and effective treatment for lung cancer. Therefore, current study was performed to elucidate the potential effects of C-terminal modulator protein (CTMP) via aerosol on lung tumorigenesis. Lentiviral vector-CTMP was delivered into K-ras null lung cancer mice through the noseonly inhalation system for 30 min. After 48 h, the potential effects of CTMP on Akt1-related signals and cell cycle regulation in the lungs were evaluated by western blot, immunohistochemistry and zymography. Lentivirus-based CTMP delivery inhibited the Akt1 activity through selective suppression of Akt1 phosphorylation at Ser473. Aerosol delivery of CTMP inhibited proteins important for Akt1 signals, cell cycle and tumor metastasis in lungs of K-ras null mice. Together, our results suggest that lentivirusmediated aerosol delivery of CTMP may be compatible with noninvasive in vivo gene therapy. Our results emphasize the importance of noninvasive-targeted delivery of CTMP for lung cancer therapy in the future. While the studies are conducted in mice, it is envisioned that noninvasive targeting the specific genes responsible for cancer progression is an attractive strategy for effective anticancer therapeutics.

Signaling mechanisms involved in altered function of macrophages from diet-induced obese mice affect immune responses

“…However, the disruption of P. gingivalis-induced Akt phosphorylation is not caused by the diminished phosphorylation of the global network of IRS proteins, because activation of JNK and p70S6K are not affected in DIO BMM⌽ after P. gingivalis infection. Therefore, we explored the ability of DIO and FFAs to induce molecules such as CTMP, PP2A, and PTEN (28)(29)(30)(31). We found that CTMP is elevated in BMM⌽ from mice with DIO, and directly inhibits Akt phosphorylation.…”

Carboxyl-Terminal Modulator Protein Positively Regulates Akt Phosphorylation and Acts as an Oncogenic Driver in Breast Cancer

“…Hwang and colleagues suggested an antitumor activity of lentivirus-mediated CTMP gene therapy by using a K-ras null lung cancer mouse model (35). Simone and colleagues indicated the pro-apoptotic function of the Figure 5.…”

Decreased Level of PDCD4 (Programmed Cell Death 4) Protein Activated Cell Proliferation in the Lung of A/J Mouse

“…(9,10) Antibodies against phospho-Akt1 (Thr308), p21, p27, CDK4, cyclinD1, PCNA, BclxL, BCL2, uPA, uPAR, PAI-1, p53, p70S6K, phospho-p70S6K (Thr 389), and actin were obtained from Santa Cruz Biotechnology (Santa Cruz, CA, USA). Phospho-p53 (Ser20), phosphomTOR (Ser 2448), eIF4E and 4E-BP1, and mTOR antibodies were obtained from Cell Signaling (Beverly, MA, USA).…”

“…For aerosol delivery, the A=J mice were exposed to an aerosol of containing lentivirus-shRNA Pdcd4 solution (50 mL) containing 40 ng=mL of lentivirus-shRNA Pdcd4 for 1 month. (10) The A=J mice were allowed to inhale the aerosolized lentivirusshRNA Pdcd4 from the nebulizer for 30 min twice a week for 1 month, after which the mice were sacrificed, and lung samples were collected for further analysis. The untreated mice and mice treated with scramble shRNA (scrambled) were used as controls.…”