Background: Myo-inositol is a nutritional supplement that has been investigated as a chemopreventive agent for lung cancer. We have investigated the effect of myo-inositol in a CC-LR (CCSPCre/LSL-K-rasG12D) mouse lung cancer model. Blood, broncho-alveolar lavage fluid (BALF), and lungs were collected from CC-LR and LR littermate control mice at 14 weeks of age, when mice had a large number of premalignant lesions with only small foci of adenocarcinoma.

Methods: Lesion burden and stage was quantified using macroscopically evident lung surface tumor counts as well as histology from paraffin sections. Serial paraffin sections were also used for immunohistochemistry. Plasma was analyzed using high-sensitivity liquid-chromatography coupled tandem mass spectrometry. Cytokine and chemokine concentrations in BALF were quantitated using multiplex immunobead assays.

Results: Myo-inositol treated mice (n = 20) had fewer tumors (p < 0.0001) than mice raised on control diet (n = 23). Additionally, lesions were shifted towards lower grade, from adenomas and adenomatous alveolar hyperplasia to bronchial hyperplasia. Several host factors including cytokines and proteins produced by myeloid derived suppressor cells and macrophages were significantly impacted by myo-inositol treatment. In addition to changes in metabolic inflammation derived factors, proteins which are associated with both chronic inflammation and lung tumorigenesis were altered as well.

Conclusions: Myo-inositol treatment both reduced tumor burden and lesion grade in a KRAS model of lung cancer. Our findings of a substantial impact of myo-inositol treatment on the host response suggests novel mechanisms for its chemopreventive activitiy.

Citation Format: Nese Unver, Kirubel T. Zeleke, Ximing Tang, Samantha Holt, Seyed Javad M. Moghaddam, Hong Wang, Ignacio I. Wistuba, Samir M. Hanash, Edwin J. Ostrin. Myo-inositol modulates the tumor microenvironment in a mouse model of lung cancer chemoprevention. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 756.