Antitumor Effects and the Compatibility Mechanisms of Herb Pair (Willd.) R. J. Wang- D. Don.

Herb pair (Willd.) R. J. Wang (HD) and D. Don (SB) has been most frequently used for cancer treatment in traditional Chinese medicine. This study aimed to explore the and antitumor effects of HD-SB extract and to elucidate the underlying compatibility mechanisms. HD, SB, and HD-SB extracts were prepared, and the components were detected by ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry method. The antitumor effects of various concentrations of these extract were detected on several tumor cell lines using MTS assay. The antitumor effects were evaluated in Panc28 cells-bearing nude mice model. The compatibility mechanisms of herb pair HD-SB were evaluated based on the systems pharmacology strategy and then validated by cellular experiments. HD-SB extract was demonstrated to inhibit the proliferation of the cancer cell lines dose dependently by MTS assay. antitumor effects of HD-SB were much more potent than either of the two single herbs in Panc28 xenograft mice model. A total 29 active ingredients involved in antitumor effects were selected from HD and SB, and the "herb-composition-target-disease" network was constructed. Then, 58 cancer-related targets and 66 KEGG pathways were identified, and PTGS2-, HSP90-, EGFR-, MMP2-, PPARγ-, and GSTP-mediated pathways were predicted to be the antitumor mechanisms of HD-SB. The cellular experiments showed that HD-SB significantly induced cancer cell apoptosis, decreased p-EGFR, HSP90 and bcl-2 expressions, and increased PPARγ, bax, cleaved caspase 3, cleaved PARP, p-AKT, and p-PI3K expressions compared with HD or SB treatment. Our study showed that HD-SB inhibited tumor growth both and , which might be related with apoptosis induction the EGFR/PPARγ/PI3K/AKT pathway.