Can Patrinia villosa water extract be taken during FOLFOX treatment in colon cancer? – evidences from a proof-of-concept preclinical study

Background 5-fluorouracil-based regimen FOLFOX (5-fluorouracil, folinic acid, oxaliplatin) is the first-line chemotherapeutic for metastatic colorectal cancer patients. On the other hand, the medicinal herb Patrinia villosa (Thunb.) Dufr. [Caprifoliaceae] is commonly prescribed by Chinese medicine practitioners to colorectal cancer patients in recent years. Thus, the possibility of concurrent use of P. villosa with FOLFOX occurs. The present study aimed to investigate whether P. villosa water extract would interfere with the metabolism and anti-tumor efficacy of chemotherapy regimen FOLFOX in preclinical colon cancer models. Methods Human HCT-116 xenograft-bearing and murine Colon-26 orthotopic tumor-bearing mouse models were established and received FOLFOX and/or PV water extract treatments for 3 weeks. FOLFOX was administered intravenously once a week and PV water extract was administered daily by oral gavage except on the FOLFOX administration day. The levels of metabolising enzymes dihydropyrimidine dehydrogenase (for 5-fluorouracil), serine hydroxymethyltransferase (for folinic acid), as well as molecules, cysteine, methionine and reduced glutathione, involved in oxaliplatin biotransformation, were determined in plasma of xenograft-bearing mice receiving FOLFOX and/or PV water extract treatment. The tumor progression, metastasis and tumor microenvironment in mice were also assessed. Results The PV water extract treatment did not affect the plasma levels of metabolising enzymes of 5-fluorouracil and folinic acid, nor the plasma levels of cysteine, methionine and reduced glutathione in HCT-116 xenograft-bearing mice. On the other hand, the combined treatment of FOLFOX and PV water extract inhibited both HCT-116 and Colon-26 tumor growth, with HCT-116 tumor weight of FOLFOX plus PV water extract group being the lowest among all treated groups. PV water extract treatment could further potentiate the anti-angiogenesis, apoptosis and immunomodulatory effect of FOLFOX in colon tumors. Conclusion This is the first report to demonstrate that no observable interference induced by PV water extract on the plasma levels of selected metabolism enzymes and precursor molecules of FOLFOX component drugs in colon tumor-bearing mice. The combined use of FOLFOX plus PV water extract resulted in better anti-tumor efficacy in colon cancer mouse models than single treatment alone. The beneficial potentials of combined use of FOLFOX and PV water extract has been scientifically verified, which supports the clinical use in colon cancer management.