Novel cancer therapy targeting microbiome

Tatsuya Nagano, Takehiro Otoshi, Daisuke Hazama, Tatsunori Kiriu, Kanoko Umezawa, Naoko Katsurada, Yoshihiro NishimuraDivision of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, JapanAbstract: In the human intestinal tract, there are more than 100 trillion symbiotic bacteria, which form the gut microbiota. Approximately 70% of the human immune system is in the intestinal tract, which prevents infection by pathogenic bacteria. When the intestinal microbiota is disturbed, causing dysbiosis, it can lead to obesity, diabetes mellitus, inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis, autism spectrum disorder and cancer. Recent metabolomics analyses have also made the association between the microbiota and carcinogenesis clear. Here, we review the current evidence on the association between the microbiota and gastric, bladder, hepatobiliary, pancreatic, lung and colorectal cancer. Moreover, several animal studies have revealed that probiotics seem to be effective for the prevention of carcinogenesis to some extent. In this review, we focused on this relationship between the microbiota and cancer, and considered how to prevent cancer using strategies involving the gut microbiota.Keywords: dysbiosis, prebiotics, probiotics, antibiotic

Synergistic interaction of gemcitabine and paclitaxel by modulating acetylation and polymerization of tubulin in non-small cell lung cancer cell lines

Wiwin Is Effendi,1,2 Tatsuya Nagano,1 Motoko Tachihara,1 Kanoko Umezawa,1 Tatsunori Kiriu,1 Ryota Dokuni,1 Masahiro Katsurada,1 Masatsugu Yamamoto,1 Kazuyuki Kobayashi,1 Yoshihiro Nishimura11Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan; 2Department of Pulmonology and Respiratory Medicine, Airlangga University Medical Faculty, Surabaya 60131, IndonesiaBackground: The combination of gemcitabine (GEM) and paclitaxel (PTX) was appealing for clinical exploration due to different mechanisms of action and partially non-overlapping toxicities.Purpose: The aim of this study was to elucidate a potential effect of this combination on the proliferation of two non-small cell lung cancer (NSCLC) cell lines, A549 and H520.Materials and methods: Cell lines were treated with GEM and PTX for 48 hours to evaluate the half maximal inhibitory concentration (IC50). To determine the combination index (CI), cell lines were exposed to GEM and PTX, in a constant ratio of IC50, by various combination treatments. GEM`s effect on tubulin was assessed by western blotting and immunofluorescent staining. GEM was combined with nanoparticle albumin-bound-paclitaxel (NP) in evaluating tumor growth inhibition.Results: The IC50 of GEM and PTX in A549 and H520 were 6.6 nM and 46.1 nM, and 1.35 nM and 7.59 nM, respectively. Among the sequences explored (GEM→PTX, PTX→GEM, and GEM plus PTX simultaneously [GEM+PTX]), GEM→PTX produced a mean CI <1 in both cell lines. Western blotting and immunofluorescent staining revealed the intention expressions of acetylated tubulin protein and enhancement of tubulin polymerization within GEM→PTX group. A combination order GEM→NP also worked synergistically to suppress tumor growth.Conclusion: The GEM→PTX sequence may represent a promising candidate regimen for the treatment of NSLCL.Keywords: IC50, combination index, tubuli