Qilian Formula Inhibits Tumor Cell Growth in a Bone Metastasis Model of Lung Cancer
Background: Bone metastasis is frequently common in advanced lung cancer with the major issue of a pathological fracture. Previous studies suggested that Astragalus membranaceus (Qi) and Ampelopsis japonica (Lian), which are used as folk medicine in China, have potential effects on inhibiting tumor...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2023-12-01
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| Series: | Integrative Cancer Therapies |
| Online Access: | https://doi.org/10.1177/15347354231217274 |
| _version_ | 1797378859180490752 |
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| author | Qin Wang MD Bei Zhao MD Jiaqi Li MD Jingwen Zhao MD Chengyan Wang PhD Quanyao Li MD Wenxiao Yang PhD Ling Xu PhD Yabin Gong PhD |
| author_facet | Qin Wang MD Bei Zhao MD Jiaqi Li MD Jingwen Zhao MD Chengyan Wang PhD Quanyao Li MD Wenxiao Yang PhD Ling Xu PhD Yabin Gong PhD |
| author_sort | Qin Wang MD |
| collection | DOAJ |
| description | Background: Bone metastasis is frequently common in advanced lung cancer with the major issue of a pathological fracture. Previous studies suggested that Astragalus membranaceus (Qi) and Ampelopsis japonica (Lian), which are used as folk medicine in China, have potential effects on inhibiting tumor growth and protecting bones, respectively. In this study, an experiment on the inhibitory effect of the Qilian formula (AAF) in vivo was designed to examine tumor growth in bone and osteoclast formation. Materials and Methods: The bone metastasis xenograft models were established by implanting NCI-H460-luc2 lung cancer cells into the right tibiae bones of mice. After confirming the model’s viability through optical imaging 7 days post-implantation, 2 groups, namely the AAF group and the control group, were administered 0.3 mL of AAF extract (9 g/kg/day) or normal saline via intragastric delivery for a duration of 4 weeks. Throughout the study, we longitudinally assessed tumor burden, bone destruction, and weight-bearing capacity in vivo using reporter gene bioluminescence imaging (BLI), micro-CT, and dynamic weight-bearing (DWB) tests. Mechanistic insights were gained through Hematoxylin-eosin (H&E) staining, immunohistochemical (IHC) analysis, western blotting, and flow cytometry. Results: Qilian formula produced significant inhibition to the progress of bone destruction and tumor burden in the right tibiae bone in the treatment group. It was further evidenced by molecular imaging in vivo via small animal micro-CT and BLI with parametric quantification, characterizing significantly lower uptake of BLI signal in the treated tumor lesions and improving the pathological changes in the microstructure of bone. Furthermore, DWB tests revealed that Qilian formula treatment significantly maintained the weight-bearing capacity. According to immunohistochemical analysis, the effect of the Qilian formula appeared to involve the suppression of osteoclast formation by lower expression of the tartrate-resistant acid phosphatase. Cell apoptosis and death induction were evidenced by a higher percentage of Bal2、BAX and caspase 3 expressions of Qilian formula-treated tumor tissues. Conclusions: Our study demonstrated a significant inhibitory effect of the Qilian formula on the progression of osteolytic invasion in vivo by suppressing osteoclastogenesis and promoting apoptotic cell death. |
| first_indexed | 2024-03-08T20:13:42Z |
| format | Article |
| id | doaj.art-0e191f67d41c47568a2df3184170eb59 |
| institution | Directory Open Access Journal |
| issn | 1552-695X |
| language | English |
| last_indexed | 2024-03-08T20:13:42Z |
| publishDate | 2023-12-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Integrative Cancer Therapies |
| spelling | doaj.art-0e191f67d41c47568a2df3184170eb592023-12-22T20:04:00ZengSAGE PublishingIntegrative Cancer Therapies1552-695X2023-12-012210.1177/15347354231217274Qilian Formula Inhibits Tumor Cell Growth in a Bone Metastasis Model of Lung CancerQin Wang MD0Bei Zhao MD1Jiaqi Li MD2Jingwen Zhao MD3Chengyan Wang PhD4Quanyao Li MD5Wenxiao Yang PhD6Ling Xu PhD7Yabin Gong PhD8Yueyang Hospital of Integrated Traditional Chinese Medicine and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaInstitute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaYueyang Hospital of Integrated Traditional Chinese Medicine and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaYueyang Hospital of Integrated Traditional Chinese Medicine and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaYueyang Hospital of Integrated Traditional Chinese Medicine and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaYueyang Hospital of Integrated Traditional Chinese Medicine and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaYueyang Hospital of Integrated Traditional Chinese Medicine and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaTumor Institute of Traditional Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaYueyang Hospital of Integrated Traditional Chinese Medicine and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaBackground: Bone metastasis is frequently common in advanced lung cancer with the major issue of a pathological fracture. Previous studies suggested that Astragalus membranaceus (Qi) and Ampelopsis japonica (Lian), which are used as folk medicine in China, have potential effects on inhibiting tumor growth and protecting bones, respectively. In this study, an experiment on the inhibitory effect of the Qilian formula (AAF) in vivo was designed to examine tumor growth in bone and osteoclast formation. Materials and Methods: The bone metastasis xenograft models were established by implanting NCI-H460-luc2 lung cancer cells into the right tibiae bones of mice. After confirming the model’s viability through optical imaging 7 days post-implantation, 2 groups, namely the AAF group and the control group, were administered 0.3 mL of AAF extract (9 g/kg/day) or normal saline via intragastric delivery for a duration of 4 weeks. Throughout the study, we longitudinally assessed tumor burden, bone destruction, and weight-bearing capacity in vivo using reporter gene bioluminescence imaging (BLI), micro-CT, and dynamic weight-bearing (DWB) tests. Mechanistic insights were gained through Hematoxylin-eosin (H&E) staining, immunohistochemical (IHC) analysis, western blotting, and flow cytometry. Results: Qilian formula produced significant inhibition to the progress of bone destruction and tumor burden in the right tibiae bone in the treatment group. It was further evidenced by molecular imaging in vivo via small animal micro-CT and BLI with parametric quantification, characterizing significantly lower uptake of BLI signal in the treated tumor lesions and improving the pathological changes in the microstructure of bone. Furthermore, DWB tests revealed that Qilian formula treatment significantly maintained the weight-bearing capacity. According to immunohistochemical analysis, the effect of the Qilian formula appeared to involve the suppression of osteoclast formation by lower expression of the tartrate-resistant acid phosphatase. Cell apoptosis and death induction were evidenced by a higher percentage of Bal2、BAX and caspase 3 expressions of Qilian formula-treated tumor tissues. Conclusions: Our study demonstrated a significant inhibitory effect of the Qilian formula on the progression of osteolytic invasion in vivo by suppressing osteoclastogenesis and promoting apoptotic cell death.https://doi.org/10.1177/15347354231217274 |
| spellingShingle | Qin Wang MD Bei Zhao MD Jiaqi Li MD Jingwen Zhao MD Chengyan Wang PhD Quanyao Li MD Wenxiao Yang PhD Ling Xu PhD Yabin Gong PhD Qilian Formula Inhibits Tumor Cell Growth in a Bone Metastasis Model of Lung Cancer Integrative Cancer Therapies |
| title | Qilian Formula Inhibits Tumor Cell Growth in a Bone Metastasis Model of Lung Cancer |
| title_full | Qilian Formula Inhibits Tumor Cell Growth in a Bone Metastasis Model of Lung Cancer |
| title_fullStr | Qilian Formula Inhibits Tumor Cell Growth in a Bone Metastasis Model of Lung Cancer |
| title_full_unstemmed | Qilian Formula Inhibits Tumor Cell Growth in a Bone Metastasis Model of Lung Cancer |
| title_short | Qilian Formula Inhibits Tumor Cell Growth in a Bone Metastasis Model of Lung Cancer |
| title_sort | qilian formula inhibits tumor cell growth in a bone metastasis model of lung cancer |
| url | https://doi.org/10.1177/15347354231217274 |
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