Investigation of the Combination Effects of Andrographis Paniculata With Chemotherapeutics for Esophageal Cancer Treatment

Abstract

Esophageal cancer (EC) is the sixthmost common cause of cancer-related deaths worldwide. Surgery is the main treatment option for EC, however, postoperative recurrence rate is high due to cancer metastasis. Even though surgery followed by adjuvant chemotherapy and concurrent radiation have shown favorable efficacies, searching for alternative adjuvant treatments—such as Chinese herbal medicines—for metastatic EC also get patients’ desire. Based on our previous screening among various Chinese herbs, Andrographis paniculata (AP) exhibited anti-tumor effect in human esophageal cancer cells. The present study therefore aimed to evaluate the anti-tumor and anti-metastasis activities of AP and the combined effects of such herbal extract with standard chemotherapeutics for EC, cisplatin and 5-fluorouracil (5-FU). Human squamous esophageal cancer (EC-109) xenograft-bearing mice model was employed to evaluate the in vivo antitumor activities. The absorption of AP water extract was determined in human intestinal Caco-2 cell monolayers. The absorbed AP components have been evaluated for their cytotoxicity using MTT assay. Our preliminary results of in vivo study showed that the number of tumor nodules was decreased in intraperitoneal xenograft-bearing mice treated with AP water extract (1600 mg/kg daily for 20 days). Besides, AP treatment also enhanced the inhibitory effects of cisplatin plus 5-FU on the number of tumor nodules. In view of our in vitro results, the absorbed AP components (APPC) showed significant cytotoxicity on EC-109. Furthermore, seven known chemical constituents were identified in the APPC for the first time, suggesting these absorbed AP components may be responsible for the activities. In conclusion, the AP water extract is effective on inhibiting tumor growth in vivo and the chemical constituents in the absorbed AP components were identified, which may further enhance the understanding of the therapeutic mechanisms of this herb. The anti-metastasis effects of AP will also be further investigated. ACKNOWLEDGEMENT: This work was supported by Food and Health Bureau HKSAR, Health and Medical Research Fund no. 11120981.