Abstract
Background & Aims: The chemotherapeutic modality comprising 5-fluorouracil (5-FU) and oxaliplatin is currently employed in treating metastatic colorectal cancer with serious drawback such as neutropenia. Nevertheless, radix Astragalus membranaceus being included in many formulations to treat immunodeficiency diseases have demonstrated effectiveness in anti-carcinogenesis. In the present investigation, we aim to study the modulating effects of
Astragalus extract on tumor formation, and to compare with that caused by the 5-FU/oxaliplatin combo using a colon tumor xenograft model.
Methods: Female athymic Balb/c nude mice were inoculated sub-axillarily with 107 viable HT-29 cells (human colonic adenocarcinoma cell line). Chemotherapeutic treatments to xenograft mice began on day 8 post-tumor cell implantation: Group 1 – control. Groups 2 & 3 – daily treatment of 2 or
4 g/kg BW Astragalus extract by gavage for 21 days. Group 4 – a single injection of oxaliplatin (10 mg/kg, i.p.) on day 8 and daily treatment of 5-FU (30 mg/kg, i.p.) for 5 consecutive days from day 8. All animals were sacrificed on day 28 after tumor xenograft. Both tumor
volume and parameters associated with apoptosis and tumor growth were determined.
Results: Tumor volume was significantly reduced in the groups of animals treated with Astragalus extract (with a reduction of 41% in the 4 g/kg group at day 28), when compared with a 52% tumor regression in the 5-FU/oxaliplatin treatment group. These antitumor
actions were in accordance with the observed pro-apoptotic effects in the respective treatment
groups (150-172% increase in apoptotic cells). In addition, there was a corresponding downregulation of the protein expression of the anti-apoptotic factor Bcl-2 and of the ornithine decarboxylase in proliferating neoplastic cells in the excised tumor tissues from all
drug-treated groups (Western analyses). Besides, both Astragalus extract and 5-FU/oxaliplatin treatments had suppressed the mRNA expression of the proto-oncogene c-myc and of the growth-related nuclear protein cyclin D1 (Real-time PCR).
Conclusion: The findings in this study envisage a potential clinical application of novel herbal medicine in colon cancer therapy, which could be developed as an adjuvant agent to be used along with a lowered
dose of the existing orthodox drugs that possess known toxicity.
Astragalus extract on tumor formation, and to compare with that caused by the 5-FU/oxaliplatin combo using a colon tumor xenograft model.
Methods: Female athymic Balb/c nude mice were inoculated sub-axillarily with 107 viable HT-29 cells (human colonic adenocarcinoma cell line). Chemotherapeutic treatments to xenograft mice began on day 8 post-tumor cell implantation: Group 1 – control. Groups 2 & 3 – daily treatment of 2 or
4 g/kg BW Astragalus extract by gavage for 21 days. Group 4 – a single injection of oxaliplatin (10 mg/kg, i.p.) on day 8 and daily treatment of 5-FU (30 mg/kg, i.p.) for 5 consecutive days from day 8. All animals were sacrificed on day 28 after tumor xenograft. Both tumor
volume and parameters associated with apoptosis and tumor growth were determined.
Results: Tumor volume was significantly reduced in the groups of animals treated with Astragalus extract (with a reduction of 41% in the 4 g/kg group at day 28), when compared with a 52% tumor regression in the 5-FU/oxaliplatin treatment group. These antitumor
actions were in accordance with the observed pro-apoptotic effects in the respective treatment
groups (150-172% increase in apoptotic cells). In addition, there was a corresponding downregulation of the protein expression of the anti-apoptotic factor Bcl-2 and of the ornithine decarboxylase in proliferating neoplastic cells in the excised tumor tissues from all
drug-treated groups (Western analyses). Besides, both Astragalus extract and 5-FU/oxaliplatin treatments had suppressed the mRNA expression of the proto-oncogene c-myc and of the growth-related nuclear protein cyclin D1 (Real-time PCR).
Conclusion: The findings in this study envisage a potential clinical application of novel herbal medicine in colon cancer therapy, which could be developed as an adjuvant agent to be used along with a lowered
dose of the existing orthodox drugs that possess known toxicity.
| Original language | English |
|---|---|
| Article number | S1245 |
| Pages (from-to) | A-178 |
| Number of pages | 1 |
| Journal | Gastroenterology |
| Volume | 128 |
| Issue number | Supplement 2, Issue 4 |
| Publication status | Published - Apr 2005 |