The synergistic antitumor effect of combined Trastuzumab and gamma interferon therapy to drug resistant Human Epidermal Growth Factor Receptor 2 (HER2) positive breast cancer cells

[Speaker] Toshihiko Gocho:1
[Co-author] Hiromichi Tsuchiya:1, Shotaro Kamijyo:1, Yoshitaka Yamazaki:2, Yui Akita:3, Yoko Ao:1, Akiko Sasaki:1, Yuji Kiuchi:1
1:Medical pharmacology, Showa University, Japan, 2:Department of Hospital Pharmaceutics, Showa University, Japan, 3:School of Pharmacy, Showa University, Japan

We reported that Trastuzumab and gamma interferon combined therapy showed higher synergistic antitumor effect than usual therapy in vitro and in vivo mouse model before.
 In this study we evaluated whether Trastuzumab and gamma interferon combined therapy shows good synergy effect to drug resistant HER2 positive human breast cancer cells or not. The resistant cell lines were made under the continuous presence of antibody. When we passage we changed the antibody culture concentration from 2microg/ml to 100microg/ml . We cultured cells until cell growth was not affected by the drug. We divided into four groups that were control group Trastuzumab group gamma interferon group Trastuzumab and gamma interferon group. Then we cultured and treat these four groups and counted cells on day3 and day7 in vitro study And we evaluated the effect in vivo mouse xenograft model. We injected resistant HER2 positive human breast cancer cells into the mouse back, treated these four groups with each drugs and measured the tumor size. And we investigated the differences of proteins, especially related to intracellular signal pathway by western blot analysis.
In vitro cell growth study and in vivo experiment the combined therapy showed higher anti-tumor effect than other groups significantly. Taken together we showed the possibility that Trastuzumab and gamma interferona therapy could be the next choice to the Trastuzumab resistant breast cancer therapy and that we could apply this gamma interferon combined therapy to antibody or molecular targeted drug resistant tumors.
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