Temozolomide and Pazopanib Combined with FOLFOX Regressed a Primary Colorectal Cancer in a Patient-derived Orthotopic Xenograft Mouse Model

Guangwei Zhu; Ming Zhao; Qinghong Han; Yuying Tan; Yu Sun; Michael Bouvet; Bryan Clary; Shree Ram Singh; Jianxin Ye; Robert M. Hoffman

Translational Oncology (Mar 2020)

Temozolomide and Pazopanib Combined with FOLFOX Regressed a Primary Colorectal Cancer in a Patient-derived Orthotopic Xenograft Mouse Model

Guangwei Zhu,
Ming Zhao,
Qinghong Han,
Yuying Tan,
Yu Sun,
Michael Bouvet,
Bryan Clary,
Shree Ram Singh,
Jianxin Ye,
Robert M. Hoffman

Affiliations

Guangwei Zhu: AntiCancer, Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA; Department of Gastrointestinal Surgery 2 Section, The First Hospital Affiliated to Fujian Medical University, Fuzhou 350005, China; Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou 350000, China
Ming Zhao: AntiCancer, Inc., San Diego, CA, USA
Qinghong Han: AntiCancer, Inc., San Diego, CA, USA
Yuying Tan: AntiCancer, Inc., San Diego, CA, USA
Yu Sun: AntiCancer, Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA
Michael Bouvet: Department of Surgery, University of California, San Diego, CA, USA
Bryan Clary: Department of Surgery, University of California, San Diego, CA, USA
Shree Ram Singh: Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD, 21702, USA; Address all correspondence to: Robert M. Hoffman, AntiCancer, Inc, 7917 Ostrow St, San Diego, CA, 92111, U.S.A. or Jian-Xin Ye, Department of Gastrointestinal Surgery 2 Section, The First Hospital Affiliated to Fujian Medical University, Fuzhou, 350005, China.20th, Chazhong Road, Fuzhou, Fujian 350005, China. or Shree Ram Singh, Basic Research Laboratory, National Cancer Institute, Frederick, MD, 21702, USA.
Jianxin Ye: Department of Gastrointestinal Surgery 2 Section, The First Hospital Affiliated to Fujian Medical University, Fuzhou 350005, China; Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou 350000, China; Address all correspondence to: Robert M. Hoffman, AntiCancer, Inc, 7917 Ostrow St, San Diego, CA, 92111, U.S.A. or Jian-Xin Ye, Department of Gastrointestinal Surgery 2 Section, The First Hospital Affiliated to Fujian Medical University, Fuzhou, 350005, China.20th, Chazhong Road, Fuzhou, Fujian 350005, China. or Shree Ram Singh, Basic Research Laboratory, National Cancer Institute, Frederick, MD, 21702, USA.
Robert M. Hoffman: AntiCancer, Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA; Address all correspondence to: Robert M. Hoffman, AntiCancer, Inc, 7917 Ostrow St, San Diego, CA, 92111, U.S.A. or Jian-Xin Ye, Department of Gastrointestinal Surgery 2 Section, The First Hospital Affiliated to Fujian Medical University, Fuzhou, 350005, China.20th, Chazhong Road, Fuzhou, Fujian 350005, China. or Shree Ram Singh, Basic Research Laboratory, National Cancer Institute, Frederick, MD, 21702, USA.

Journal volume & issue: Vol. 13, no. 3

Abstract

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Purpose: The goal of the present study was to determine the efficacy of temozolomide (TEM) and pazopanib (PAZ) combined with FOLFOX (oxaliplatin, leucovorin and 5-fluorouracil) on a colorectal cancer patient-derived orthotopic xenograft (PDOX) mouse model. Materials and Methods: A colorectal cancer tumor from a patient previously established in non-transgenic nude mice was implanted subcutaneously in transgenic green fluorescence protein (GFP)-expressing nude mice in order to label the tumor stromal cells with GFP. Then labeled tumors were orthotopically implanted into the cecum of nude mice. Mice were randomized into four groups: Group 1, untreated control; group 2, TEM + PAZ; group 3, FOLFOX; group 4, TEM + PAZ plus FOLFOX. Tumor width, length, and mouse body weight were measured weekly. The Fluor Vivo imaging System was used to image the GFP-lableled tumor stromal cells in vivo. H&E staining and immunohistochemical staining were used for histological analysis. Results: All three treatments inhibited tumor growth as compared to the untreated control group. The combination of TEM + PAZ + FOLFOX regressed tumor growth significantly more effectively than TEM + PAZ or FOLFOX. Only the combination of TEM + PAZ + FOLFOX group caused a decrease in body weight. PAZ suppressed lymph vessels density in the colorectal cancer PDOX mouse model suggesting inhibition of lymphangiogenesis. Conclusion: Our results suggest that the combination of TEM + PAZ + FOLFOX has clinical potential for colorectal cancer patient.

Published in Translational Oncology

ISSN: 1944-7124 (Print); 1936-5233 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.journals.elsevier.com/translational-oncology/

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