br Conclusion br In summary we built a multi
In summary, we built a multi-organ microfluidic bionic chip platform to study lung cancer BM, and verified its effectiveness using lung cancer Filipin III with differing metastatic abilities. Our study also demonstrated that AKR1B10 was significantly elevated in lung cancer-derived BM. AKR1B10 promoted the disassembly of the BBB to facilitate the trans-endothelial migration of tumor cells, possibly by up-regulating MMP-2 and MMP-9 expression mediated by a MEK/ERK signaling pathway.
WWL and JS conceived all aspects of this study, chip design and set-up, animal studies, participated in all other experiments and prepared the manuscript. XHD, YZ and YL assisted with the design and fabrication of chip. RL assisted with q-PCR, western blot, enzyme-linked immunosorbent assay. LL and YTH assisted with collection of clinical specimens. JXH and JB assisted with immunofluorescence assays and cell culture studied. HBS, WW and QW designed and supervised the experiment.
Conflicts of interest
There are no conflicts to declare.
Appendix A. Supplementary data
expression of alpha5-integrin and the activation of Src, Ras and Erk, Oncogene
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AKT1-targeted proapoptotic activity of compound K in human breast cancer cells
Eunju Choi, Eunji Kim, Ji Hye Kim, Keejung Yoon, Sunggyu Kim, Jongsung Lee, Jae Youl Cho
To appear in:
Journal of Ginseng Research
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Metabolism Compound K AKT1
1 AKT1-targeted proapoptotic activity of compound K in human breast
2 cancer cells
7 1 Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, 8 Republic of Korea
9 2 Research and Business Foundation, Sungkyunkwan University, Suwon 16419, Korea
10 11 Short title: AKT1-targeted proapoptotic activity of compound K
12 13 a: These authors equally contributed to this work. 14 15 *, ** Corresponding authors. Department of Integrative Biotechnology, Sungkyunkwan
23 Background: Breast cancer is a severe disease and the second leading cause of cancer death
24 in women worldwide. To surmount this, various diagnosis and treatment options for breast
25 cancer have been developed. One of the most effective strategies for cancer treatment is to
26 induce apoptosis using naturally occurring compounds. Compound K (CK) is a ginseng
27 saponin metabolite generated by human intestinal bacteria. CK has been studied for its
28 cardioprotective, anti-inflammatory, and liver protection effects; however, the role of CK in
29 breast cancer is not fully understood.
30 Methods: To investigate the anti-cancer effects of CK in SKBR3 and MDA-MB-231 cells,
31 cell viability assays and flow cytometry analysis were employed. In addition, the direct
32 targets of CK anti-cancer activity were identified using immunoblotting analysis and
33 overexpression experiments. Invasion, migration, and clonogenic assays were carried out to
34 determine the effects of CK on cancer metastasis.
35 Results: CK induced cell apoptosis in SKBR3 cells as determined through MTT assays, PI
36 and annexin V staining, and morphological changes. CK increased the cleaved forms of
38 the cell survival pathway, CK activated only AKT1 and not AKT2. Moreover, CK inhibited
39 breast cancer cell invasion, migration, and colony formation. Through regulation of AKT1