Xin Zhang1,2, Jiandong Wang1, Yali Fan1,2, Ziyi Zhao1,2, Sarah E Paraghamian2, Gabrielle M Hawkins2, Lindsey Buckingham2, Jillian O'Donnell2, Tianran Hao2, Hongyan Suo1,2, Yajie Yin2, Wenchuan Sun2, Weimin Kong1, Delin Sun3, Luyu Zhao4, Chunxiao Zhou5,6, Victoria L Bae-Jump7,8. 1. Department of Gynecologic Oncology, Beijing Obstetrics and Gynecology Hospital, Beijing Maternal and Child Health Care Hospital, Capital Medical University, Beijing, 100026, People's Republic of China. 2. Division of Gynecologic Oncology, University of North Carolina at Chapel Hill, 170 Manning Dr, Chapel Hill, NC, 27599, USA. 3. Shandong Juxinyuan Asparagus Industry Development Research Institute, HeZe, 274400, Shandong, People's Republic of China. 4. Shandong Juxinyuan Agricultural Technology Co. LTD, HeZe, 274400, Shandong, People's Republic of China. 5. Division of Gynecologic Oncology, University of North Carolina at Chapel Hill, 170 Manning Dr, Chapel Hill, NC, 27599, USA. czhou@med.unc.edu. 6. Division of Gynecologic Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, 450 West Dr, Chapel Hill, NC, 27599, USA. czhou@med.unc.edu. 7. Division of Gynecologic Oncology, University of North Carolina at Chapel Hill, 170 Manning Dr, Chapel Hill, NC, 27599, USA. victoria_baejump@med.unc.edu. 8. Division of Gynecologic Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, 450 West Dr, Chapel Hill, NC, 27599, USA. victoria_baejump@med.unc.edu.
Abstract
PURPOSE: Although paclitaxel is a promising first-line chemotherapeutic drug for ovarian cancer, acquired resistance to paclitaxel is one of the leading causes of treatment failure, limiting its clinical application. Asparagus officinalis has been shown to have anti-tumorigenic effects on cell growth, apoptosis, cellular stress and invasion of various types of cancer cells and has also been shown to synergize with paclitaxel to inhibit cell proliferation in ovarian cancer. METHODS: Human ovarian cancer cell lines MES and its PTX-resistant counterpart MES-TP cell lines were used and were treated with Asparagus officinalis and paclitaxel alone as well as in combination. Cell proliferation, cellular stress, invasion and DMA damage were investigated and the synergistic effect of a combined therapy analyzed. RESULTS: In this study, we found that Asparagus officinalis combined with low-dose paclitaxel synergistically inhibited cell proliferation, induced cellular stress and apoptosis and reduced cell invasion in paclitaxel-sensitive and -resistant ovarian cancer cell lines. The combined treatment effects were dependent on DNA damage pathways and suppressing microtubule dynamics, and the AKT/mTOR pathway and microtubule-associated proteins regulated the inhibitory effect through different mechanisms in paclitaxel-sensitive and -resistant cells. CONCLUSION: These findings suggest that the combination of Asparagus officinalis and paclitaxel have potential clinical implications for development as a novel ovarian cancer treatment strategy.
PURPOSE: Although paclitaxel is a promising first-line chemotherapeutic drug for ovarian cancer, acquired resistance to paclitaxel is one of the leading causes of treatment failure, limiting its clinical application. Asparagus officinalis has been shown to have anti-tumorigenic effects on cell growth, apoptosis, cellular stress and invasion of various types of cancer cells and has also been shown to synergize with paclitaxel to inhibit cell proliferation in ovarian cancer. METHODS: Human ovarian cancer cell lines MES and its PTX-resistant counterpart MES-TP cell lines were used and were treated with Asparagus officinalis and paclitaxel alone as well as in combination. Cell proliferation, cellular stress, invasion and DMA damage were investigated and the synergistic effect of a combined therapy analyzed. RESULTS: In this study, we found that Asparagus officinalis combined with low-dose paclitaxel synergistically inhibited cell proliferation, induced cellular stress and apoptosis and reduced cell invasion in paclitaxel-sensitive and -resistant ovarian cancer cell lines. The combined treatment effects were dependent on DNA damage pathways and suppressing microtubule dynamics, and the AKT/mTOR pathway and microtubule-associated proteins regulated the inhibitory effect through different mechanisms in paclitaxel-sensitive and -resistant cells. CONCLUSION: These findings suggest that the combination of Asparagus officinalis and paclitaxel have potential clinical implications for development as a novel ovarian cancer treatment strategy.
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