Bleomycin (BLM), a family of anti-
tumor drugs, was reported to exhibit severe side effects limiting its usage in clinical treatment. Therefore, finding adjuvants that enhance the anti-
tumor effect and reduce the detrimental effect of BLM is a prerequisite. Chrysanthemum indicum, an edible flower, possesses abundant bioactivities; the supercritical-
carbon dioxide fluid extract from flowers and buds of C. indicum (CISCFE) have strong anti-inflammatory,
anti-oxidant, and lung protective effects. However, the role of CISCFE combined with BLM treatment on
tumor-bearing mice remains unclear. The present study aimed to investigate the potential synergistic effect and the underlying mechanism of CISCFE combined with BLM in the treatment of
hepatoma 22 (H22)
tumor-bearing mice. The results suggested that the
oral administration of CISCFE combined with BLM could markedly prolong the life span, attenuate the BLM-induced
pulmonary fibrosis, suppress the production of pro-inflammatory
cytokines (interleukin-6),
tumor necrosis factor-α, activities of
myeloperoxidase, and malondiadehyde. Moreover, CISCFE combined with BLM promoted the
ascites cell apoptosis, the activities of
caspases 3 and 8, and up-regulated the
protein expression of p53 and down-regulated the transforming growth factor-β1 by activating the gene expression of
miR-29b. Taken together, these results indicated that CISCFE could enhance the anti-
cancer activity of BLM and reduce the BLM-induced
pulmonary injury in H22
tumor-bearing mice, rendering it as a potential adjuvant drug with
chemotherapy after further investigation in the future.