Xiao-Ai-Ping Injection Enhances Effect of Paclitaxel to Suppress Breast Cancer Proliferation and Metastasis via Activating Transcription Factor 3

Abstract

Chemotherapy is an effective treatment for invasive breast cancer. Paradoxically, many recently published findings showed that the first-line chemotherapeutic agent paclitaxel (PTX) showed pro-metastatic effects in the progress of treating breast cancer. Xiao-Ai-Ping (XAP) injection, composed of a traditional herbal medicine, Marsdenia tenacissimae extract, is known to exert antitumor effects on various cancers. However, there are few experimental studies on breast cancer. The underlying mechanism of the antitumor effect of XAP combined with chemotherapy agents has not been fully understood. In the present study, we sought to find the antitumor effects of XAP combined with PTX in vitro and in vivo. The data demonstrated that the combination of XAP with PTX resulted in remarkable enhancement of the pro-apoptotic, migration-inhibiting, and anti-invasive effects of PTX in vitro. Significantly, further study showed the overexpression of ATF3 in PTX-treated cell, while XAP counteracted the change of ATF3 induced by PTX. Moreover, it showed that combination treatment could promote the inhibition of tumor growth in MDA-MB-231 cell xenograft mouse model. Compared with PTX treatment, the downregulation of ATF3 indicated that ATF3 played a pivotal role in the combination of XAP with PTX to exert a synergistic effect. Overall, it is expected that PTX combined with XAP may serve as an effective agent for antitumor treatment, and dampening ATF3 maybe a potential strategy to improve the efficacy of PTX.

Integrating Chinese medicine into mainstream cancer therapies: a promising future

“…In vivo , experiments also confirmed that the combination enhanced the inhibitory effect on tumor cells. These results suggest that XAP enhances PTX efficacy by inhibiting ATF3 ( 148 ). TNBC is a special subtype of breast cancer and is a refractory tumor.…”

Polyoxypregnanes as safe, potent, and specific ABCB1-inhibitory pro-drugs to overcome multidrug resistance in cancer chemotherapy in vitro and in vivo

“…Firstly, Xiao-ai-ping alone (particularly via injection route) exhibits direct anticancer effect in different cancer cell lines and animal tumor xenografts 47 , 48 . Secondly, the injectable Xiao-ai-ping enhances the antitumor effects of several anticancer drugs through various mechanisms including the inhibition of CYP3A4 activity, downregulation of activating transcription factor 3 (ATF3), and suppression of pregnane X receptor (PXR) expression and downstream targets 49 , 50 , 51 . Moreover, our research team also reported that several POPs in M. tenacissima inhibited the MDR ABC transporters and potentiated the cytotoxic effect of chemotherapeutic drugs previously 24 .…”

Bioinformatic analysis and experimental validation of six cuproptosis-associated genes as a prognostic signature of breast cancer

“…Clinically, some BRCA treatments, like mastectomy, chemotherapy, and radiotherapy, have serious side effects ( Miller et al, 2016 ). Chemotherapy is more effective than mastectomy and radiotherapy for metastatic cancer ( Chen et al, 2020 ); however, conventional chemotherapeutic drugs are associated with serious side effects such as neutropenia, stomatitis, and mucositis ( Hesketh Paul et al, 2004 ). Nanoparticle-based cancer vaccines are currently being developed and are in the early stages ( Wen et al, 2019 ).…”