Xiaolin Zi

picture of Xiaolin  Zi

Professor, Urology
School of Medicine
Joint Appointment, Pharmaceutical Sciences

Joint Appointment, Pharmacology
School of Medicine

M.S., McGill University, 2003, Biostatistics
Ph.D., Shanghai Medical University, 1995, Epidemiology

Phone: (714) 456-8316
Fax: (714) 456-1679
Email: xzi@uci.edu

University of California, Irvine
Chao Cancer Center, 4th Floor
101 The City Drive South
Irvine, CA 92868
Research Interests
Natural products, molecular targets, cancer prevention and treatment
Research Abstract
Dr. Zi combines knowledge in population science with laboratory skills in basic science to develop clinically useful and less or non-toxic bioactive agents from edible plant products for cancer prevention and treatment. His publications identifying silibinin as a strong antiproliferative and differentiate agent for prostate cancer cells have resulted in a Phase 2 clinical trial of silibinin in prostate cancer patients. His NIH funded research discovered that lycopene supplementation can enhance anti-tumor efficacy of docetaxel in prostate cancer mouse xenograft model. The study on lycopene and docetaxel combination in treatment of castration-resistant prostate cancer is also now in Phase I clinical trial at the UCI.

Dr. Zi’s research team studies the efficacy and mechanism of active components of the Kava plant for prevention of tobacco-related bladder cancer using mouse carcinogenesis models. They are developing Ultra Performance Liquid Chromatograph (UPLC)-MS/MS, Chip-sequence, microarray and other molecular biology techniques (e.g., transfection and RNA interference) to study the role of tobacco-related bladder carcinogens and Kava chemicals in histone lysine methylation and epigenetic gene regulation, leading to carcinogenic and anti-carcinogenic effects.

Dr. Zi’s research team also investigates the role of Wnt signaling pathway in the resistance of anti-angiogenic cancer therapy and examine the usefulness of secreted Wnt antagonists for improving the efficacy of  bevacizumab in treatment of prostate cancer.
Zi X, Grasso AW, Kung H-J, Agarwal R. A flavonoid antioxidant silymarin inhibits activation of erbB1 signaling, and induces cyclin-dependent kinase inhibitors, G1 arrest and anti-carcinogenic effects in human prostate carcinoma cells DU145. Cancer Res, 58:1920-1929, 1998.

Zi X, Agarwal R. Silibinin decreases prostate specific antigen levels with cell growth inhibition via G1 arrest, leading to differentiation of prostate carcinoma cells: Implications for prostate cancer intervention. Proc Natl Acad Sci USA, 96: 7490-7495, 1999.

Zi X, Zhang J., Agarwal R, Pollak M. Silibinin up-regulates insulin-like growth factor-binding protein 3 expression and inhibits proliferation of androgen-independent prostate cancer cells Cancer Res 60:5617-20, 2000.

Zi X, Singh RP, Agarwal R. Impairment of erbB1 receptor and fluid-phase endocytosis and associated mitogenic signaling by inositol hexaphosphate in human prostate carcinoma DU145 cells. Carcinogenesis, 21:2225-35. 2000.

Lu Y, Zi X, Zhao Y, Pollak M. Insulin-like growth factor-I receptor signalling and resistance to transtuzumab (Herceptin). J Natl Cancer Inst 93:1852-7, 2001.

Lu Y, Zi X, Pollak M. Molecular mechanisms underlying IGF-I-induced attenuation of the growth inhibitory activity of trastuzumab (Herceptin) on SKBR3 breast cancer cells. Int J Cancer 108:334-41, 2004.

Lu Y, Zi X, Zhao Y, Pollak M. Overexpression of ErbB2 receptor inhibits IGF-I-induced Shc-MAPK signaling pathway in breast cancer cells. Biochem Biophys Res Commun 313: 709-715, 2004.

Zi X, Simoneau A. Flavokawain A, a novel chalcone from Kava Extract, induces apoptosis in bladder cancer cells by involvement of bax protein-dependent and mitochondria-dependent apoptotic pathway and suppresses tumor growth in mice. Cancer Res 65: 3479-3486, 2005.

Zi X, Guo Y, Simoneau A, Christopher H, Xie J, Holcombe RH, Hoang BH. Expression of Frzb/sFRP3, a secreted Wnt antagonist, in an androgen-independent prostate cancer cellular model suppresses tumorigenesis and invasiveness. Cancer Res. 65:9762-70, 2005Liu B, Lee KW, Anzo M, Zhang B, Zi X, Tao Y, Shiry L, Pollak M, Lin S, Cohen P. Insulin-like growth factor-binding protein-3 inhibition of prostate cancer growth involves suppression of angiogenesis. Oncogene 26:1811-9, 2007.

Guo Y, Zi X, Koontz Z, Kim A, Xie J, Gorlick R, Holcombe RF, Hoang BH. Blocking Wnt/LRP5 signaling by a soluble receptor modulates the epithelial to mesenchymal transition and suppresses met and metalloproteinases in osteosarcoma Saos-2 cells. J Orthop Res 25: 964-71, 2007.

Tang Y, Simoneau AR, Xie J, Shahandeh B, Zi X. Flavokawain A, a novel chalcone from Kava extract, differentially induces G1 and M phase arrests in human urinary bladder cancer cell lines associated with their p53 status. Cancer Prev Res (Phila Pa). 1:439-51, 2008 .

Guo Y, Xie J, Rubin E, Zi X, Hoang BH. Frzb, a Secreted Wnt Antagonist, Decreases Growth and Invasiveness of Soft Tissue Sarcoma Cells, Associated with Inhibition of Met Signaling. Cancer Res 68: 3350-60, 2008.

Guo Y, Xie J, Rubin E, Zi X, Hoang BH. Dominant Negative LRP5 Decreases Tumorigenicity and Metastasis of Osteosarcoma. Clinical Orthopaedics and Related Research 466:2039-45, 2008.

Tang Y, Simoneau AR, Liao W, Guo Y, Hoang BH, Hope C, Liu F, Li S, Xie J, Holcombe RF, Jurnak FA, Mercola D, Zi X. WIF-1, a Wnt pathway inhibitor, inhibits the in vitro and in vivo growth of human invasive urinary bladder cancer cells by induction of G1 arrest. Mol Cancer Ther 8:458-68, 2009

Tang Y, Li X, Liu Z, Simoneau AR, Xie J, Zi X. Flavokawain B, a kava chalcone, exhibits robust apoptotic mechanisms on androgen receptor-negative, hormone-refractory prostate cancer cell lines and reduces tumor growth in a preclinical model. Int J Cancer 2010;127:1758-68. PMCID: PMC Journal – In Process.

Rubin E, Guo Yi, Tu K, Xie J, Zi X, Hoang BH. Wnt Inhibitory Factor 1 (WIF-1) decreases tumorigenesis and metastasis in osteosarcoma. Mol Cancer Ther 2010 9:731-41. PMCID: PMC Journal – In Process.

Yee DS, Tang Y, Li X, Liu Z, Guo Y, Ghaffar S, McQueen P, Atreya D, Xie J, Simoneau AR, Hoang BH, Zi X. The Wnt inhibitory factor 1 restoration in prostate cancer cells was associated with reduced tumor growth, decreased capacity of cell migration and invasion and a reversal of epithelial to mesenchymal transition. Mol Cancer 2010;9:162.

Tang Y, Simoneau AR, Parmakhtiar B, Simoneau AR, Xie J, Fruehauf J, Lilly M, Zi X. Lycopene enhances docetaxel’s effect in castration-resistant prostate cancer associated with insulin-like growth factor I receptor levels. Neoplasia 2011;13:108-19.

Liu Z, Li X, Simoneau AR, Jafari M, Zi X. Rhodiola rosea extracts and salidroside decrease the growth of bladder cancer cell lines via inhibition of the mTOR pathway and induction of autophagy. Mol Carcinog 2011 [Epub ahead of print]
1 R01 CA122558-01A2 (Zi) 12/01/07-11/30/12, NIH/NCI, Amount: $1,934,930 Chemoprevention of urinary bladder carcinogenesis by flavokawain A.
3R01CA122558-03S1 (Zi) 8/1/2010-11/30/2011 NIH/NCI, Amount: $176,851 Title: Chalcone analogues for targeting p53 mutant ovarian cancer cells.
1R21CA152804-01A1 (Zi) 04/01/2011-03/31/2013, NIH/NCI, Amount: $ 420,750, Title: Rhodiola Rosea Extracts, Salidroside and Bladder Cancer Chemoprevention.
PC100869 (Zi)09/01/2011-8/30/2014,DOD/Prostate Cancer Research Program, Amount: $573,749, Title: Co-targeting VEGF and Neuropilins with bevacizumab and secreted Wnt inhibitors in prostate cancer.
UCI Institute for clinical and translational sciences pilot award(Zi) 12/6/2010 - 3/31/2011, Amount: $29,000 Title: Inhibition of pro-invasive effects of anti-VEGF therapy by secreted Wnt antagonists.
Graduate Programs
Medicinal Chemistry and Pharmacology

Pharmacological Sciences

Research Center
Chao Family Comprehensive Cancer Center
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