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Tumor-suppressor effects of chemical functional groups in an in vitro co-culture system

Frontiers of Materials Science 2014年第2期8卷 136-141页

作者： Su-Ju xu Fu-Zhai CUI Xiang-Dong KONG Institute of Biomaterials and Marine Biological Resources College of Life Sciences Zhejiang Sci-Tech University Hangzhou 310018 China Institute of Regenerative Medicine and Biomimetic Materials School of Materials Science and Engineering Tsinghua University Beijing 100084 China

Liver normal cells and cancer cells co-cultured on surfaces modified by different chemical functional groups, including mercapto （-SH）, hydroxyl （-OH） and methyl （-CHz） groups. The results showed that different cells exhibited changes in response to different surfaces. Normal cells on -SH surface exhibited the smallest contact area with mostly rounded morphology, which led to the death of cancer cells, while cancer cells could not grow on -CH3 groups, which also died. In the co-culture system, the -CH3 group exhibited its unique effect that could trigger the death of cancer cells and had no effects on normal cells. Our findings provide useful information on strategies for the design of efficient and safe regenerative medicine materials.

关键词： tumor suppressor chemical functional group co-culture system regen-erative medicine material

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Steroid Sulfatase Inhibitor Reduces Proliferation of Ishikawa Endometrial Cancer Cells in co-culture systems

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Open Journal of Endocrine and Metabolic Diseases 2016年第9期6卷 193-204页

作者： Mitsuo Nishimoto Masafumi Toyoshima Naomi Shiga Hiroki Utsunomiya Fumihiko Suzuki Satoru Nagase Hidekazu Nishigori Takashi Suzuki Hironobu Sasano Kiyoshi Ito Nobuo Yaegashi Department of Obstetrics and Gynecology Tohoku University School of Medicine Sendai Japan Department of Obstetrics and Gynecology Iwate Prefectural Iwai Hospital Iwate Japan Department of Obstetrics and Gynecology Yamagata University School of Medicine Yamagata Japan Department of Pathology Tohoku University School of Medicine Sendai Japan Department of Disaster Obstetrics and Gynecology International Research Institute of Disaster Science Tohoku University Sendai Japan

Objectives: Estrogens significantly contribute toward the growth and development of endometrial cancers. Two principal pathways have been implicated in the final steps of estrogen synthesis: the steroid sulfatase (STS) and aromatase pathways. In this study, we aimed to evaluate the possible effects of tumor-stromal interactions on local estrogen biosynthesis in endometrial cancer. We also assessed the biological effects of inhibitors of steroid sulfatase and aromatase in the co-culture system compared with usual monocultures. Methods/Materials: We isolated stromal cells from endometrial cancer patients to examine local biosynthesis of estrogens and tumor-stromal interactions. Next we examined the effects of steroid sulfatase inhibitor and aromatase inhibitor in monoculture of endometrial cancer cell line (Ishikawa) and in a co-culture system involving an Ishikawa cells and stromal cells. Results: Estrogen receptor and steroid sulfatase mRNA levels in cancer cells were significantly higher in the co-cultures compared with the monocultures of endometrial cancer cells. Estradiol and androstenediol concentrations were also significantly higher in the co-cultured cells. Proliferation of the cancer cells was significantly increased through the steroid sulfatase pathway, which metabolizes androgens, estrone sulfate, and estradiol sulfate as its substrates. However, its proliferation was significantly decreased by the treatment of steroid sulfatase or aromatase inhibitors. The significant growth inhibition by the steroid sulfatase and aromatase inhibitors were also observed in the co-culture system. conclusions: We evaluated the effects of STS inhibitor and aromatase inhibitors on the proliferation of estrogen-dependent endometrial cancer cells. considering that intratumoral estrogen metabolism plays an important role, our co-culture systems provide an environment similar to that of the tumor in living patients in terms of metabolism and synthesis of intratumoral estrogens.

关键词： Aromatase Inhibitors co-culture system Endometrial Cancer Estrogen Estrogen Sulfatase Inhibitor

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