JP2020152679A - Prophylactic or therapeutic agents for breast cancer and growth inhibitors of breast cancer cells - Google Patents
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Abstract
Description
本発明の一態様は、乳がんの予防又は治療剤に関する。
本発明の他の一態様は、乳がん細胞の増殖抑制剤に関する。
One aspect of the present invention relates to a prophylactic or therapeutic agent for breast cancer.
Another aspect of the present invention relates to an agent for suppressing the growth of breast cancer cells.
わが国の２０１３年の乳がん死亡数は女性約１３，０００人で、女性ではがん死亡全体の約９％を占める。２０１１年の女性乳がんの罹患数は、全国推計値約７２，５００例であり、女性のがん罹患全体の約２０％を占めている。乳がんの治療は、外科的治療、放射線治療、薬物療法（ホルモン療法、化学療法、分子標的治療など）があり、それらを単独ないし複数で行われている。しかし、根治が難しい場合があるのに加え、乳房を取り除く手術を拒否する患者も少なくない。ＨＥＲ２陽性乳がんは、進行が速い上、再発率が高く予後が悪い。ＨＥＲ２陽性乳がんの治療法として、分子標的薬トラスツズマブ（Ｔｒａｓｔｕｚｕｍａｂ）を用いた治療法が開発されている。 The number of breast cancer deaths in Japan in 2013 was about 13,000 women, accounting for about 9% of all cancer deaths among women. The number of female breast cancer cases in 2011 is estimated to be about 72,500 cases nationwide, accounting for about 20% of all female cancer cases. Treatment of breast cancer includes surgical treatment, radiation therapy, and drug therapy (hormone therapy, chemotherapy, molecular targeted therapy, etc.), which are performed individually or in combination. However, in addition to being difficult to cure, many patients refuse surgery to remove the breast. HER2-positive breast cancer progresses rapidly, has a high recurrence rate, and has a poor prognosis. As a therapeutic method for HER2-positive breast cancer, a therapeutic method using the molecular-targeted drug trastuzumab has been developed.
一方、２−ヒドロキシ−１，４−ナフトキノンは「Ｌａｗｓｏｎｅ」と呼ばれる化合物である。非特許文献１では、Ｌａｗｓｏｎｅがヒト大腸がん細胞であるＤＬＤ−１細胞の増殖を抑制する作用を有することが報告されている。非特許文献２では、Ｌａｗｓｏｎｅの類似体が抗癌活性を有することが記載されている。 On the other hand, 2-hydroxy-1,4-naphthoquinone is a compound called "Lawsone". Non-Patent Document 1 reports that Lawsone has an action of suppressing the proliferation of DLD-1 cells, which are human colon cancer cells. Non-Patent Document 2 describes that Lawsone analogs have anti-cancer activity.
トラスツズマブ等の抗ＨＥＲ２抗体を用いたＨＥＲ２陽性乳がんの治療法の有効性は個人差が大きく、副作用の可能性もある。また、再発がんの約２０％で遠隔転移が認められ、脳転移の場合、トラスツズマブは適応外となる。
また、トラスツズマブ等の抗ＨＥＲ２抗体はＨＥＲ２を標的とする抗体医薬であるため、ＨＥＲ２陰性乳がんの予防又は治療に用いることはできない。
そこで本発明は、単独で又は抗ＨＥＲ２抗体と併用して広範に使用できる乳がんの予防又は治療剤を提供することを目的とする。
The effectiveness of treatment for HER2-positive breast cancer using anti-HER2 antibodies such as trastuzumab varies greatly among individuals, and there is a possibility of side effects. In addition, distant metastasis is observed in about 20% of recurrent cancers, and trastuzumab is not indicated for brain metastasis.
Moreover, since anti-HER2 antibodies such as trastuzumab are antibody drugs that target HER2, they cannot be used for the prevention or treatment of HER2-negative breast cancer.
Therefore, an object of the present invention is to provide a prophylactic or therapeutic agent for breast cancer that can be widely used alone or in combination with an anti-HER2 antibody.
本発明者らは、２−ヒドロキシ−１，４−ナフトキノン（Ｌａｗｓｏｎｅ）が、ＨＥＲ２陽性乳がん細胞だけでなくＨＥＲ２陰性乳がん細胞の増殖を抑制することができること、並びに、２−ヒドロキシ−１，４−ナフトキノンと抗ＨＥＲ２抗体との組み合わせがＨＥＲ２陽性乳がん細胞の増殖を抑制することができ、抗ＨＥＲ２抗体の投与量を低減することができることを見出し、本発明を完成するに至った。 We found that 2-hydroxy-1,4-naphthoquinone (Lawsone) can suppress the growth of not only HER2-positive breast cancer cells but also HER2-negative breast cancer cells, and 2-hydroxy-1,4-. We have found that the combination of naphthoquinone and an anti-HER2 antibody can suppress the growth of HER2-positive breast cancer cells and reduce the dose of the anti-HER2 antibody, and have completed the present invention.
本発明は第一に、２−ヒドロキシ−１，４−ナフトキノン及び／又はその薬学的に許容される塩を有効成分として含有する乳がんの予防又は治療剤に関する。
本発明の乳がんの予防又は治療剤は、トラスツズマブ等の抗ＨＥＲ２抗体の投与を受ける動物に投与する用途に用いることができる。
The present invention first relates to a prophylactic or therapeutic agent for breast cancer containing 2-hydroxy-1,4-naphthoquinone and / or a pharmaceutically acceptable salt thereof as an active ingredient.
The prophylactic or therapeutic agent for breast cancer of the present invention can be used for administration to animals receiving anti-HER2 antibody such as trastuzumab.
本発明は第二に、抗ＨＥＲ２抗体、並びに、２−ヒドロキシ−１，４−ナフトキノン及び／又はその薬学的に許容される塩を含有する乳がんの予防又は治療剤に関する。
この発明に係る乳がんの予防又は治療剤によれば、抗ＨＥＲ２抗体と、２−ヒドロキシ−１，４−ナフトキノン及び／又はその薬学的に許容される塩の、それぞれの投与量を低減することができる。このため各成分に対する副作用の症状がみられる動物において副作用を低減することができる。
The present invention secondly relates to anti-HER2 antibodies and prophylactic or therapeutic agents for breast cancer containing 2-hydroxy-1,4-naphthoquinone and / or pharmaceutically acceptable salts thereof.
According to the prophylactic or therapeutic agent for breast cancer according to the present invention, it is possible to reduce the respective doses of the anti-HER2 antibody and 2-hydroxy-1,4-naphthoquinone and / or a pharmaceutically acceptable salt thereof. it can. Therefore, side effects can be reduced in animals that have side effects on each component.
本発明は第三に、２−ヒドロキシ−１，４−ナフトキノン及び／又はその薬学的に許容される塩を有効成分として含有する乳がん細胞の増殖抑制剤に関する。 The present invention relates to a growth inhibitor for breast cancer cells containing 2-hydroxy-1,4-naphthoquinone and / or a pharmaceutically acceptable salt thereof as an active ingredient.
本発明の乳がんの予防又は治療剤は、トラスツズマブ等の抗ＨＥＲ２抗体と併用してＨＥＲ２陽性乳がんを予防又は治療するために用いることができる。本発明の乳がんの予防又は治療剤は、また、抗ＨＥＲ２抗体が有効でないＨＥＲ２陰性乳がんを予防又は治療するために用いることもできる。
本発明の乳がん細胞の増殖抑制剤は、ＨＥＲ２陽性乳がん細胞及びＨＥＲ２陰性乳がん細胞の両方の乳がん細胞の増殖を抑制することができる。
The breast cancer prophylactic or therapeutic agent of the present invention can be used in combination with an anti-HER2 antibody such as trastuzumab to prevent or treat HER2-positive breast cancer. The breast cancer prophylactic or therapeutic agent of the present invention can also be used to prevent or treat HER2-negative breast cancer for which anti-HER2 antibody is ineffective.
The breast cancer cell growth inhibitor of the present invention can suppress the growth of both HER2-positive breast cancer cells and HER2-negative breast cancer cells.
２−ヒドロキシ−１，４−ナフトキノン（Ｌａｗｓｏｎｅ）は以下の構造式で表される化合物である。２−ヒドロキシ−１，４−ナフトキノンを以下の説明では「Ｌａｗｓｏｎｅ」と称する。 2-Hydroxy-1,4-naphthoquinone (Lawsone) is a compound represented by the following structural formula. 2-Hydroxy-1,4-naphthoquinone is referred to as "Lawsone" in the following description.
Ｌａｗｓｏｎｅの薬学的に許容される塩の種類は特に限定されないが、例えばナトリウム塩、カリウム塩等のアルカリ金属塩；カルシウム塩、マグネシウム塩等のアルカリ土類金属塩；アンモニウム塩；アルギニン、リジン、ヒスチジン、オルニチン等の塩基性アミノ酸塩；モノエタノールアミン塩、ジエタノールアミン塩等のアミン塩等が挙げられる。これらの塩は１種単独で使用してもよいし、２種以上の組合せを使用してもよい。 The type of pharmaceutically acceptable salt of Lawsone is not particularly limited, but for example, alkali metal salts such as sodium salt and potassium salt; alkaline earth metal salts such as calcium salt and magnesium salt; ammonium salt; arginine, lysine and histidine. , Ornithine and other basic amino acid salts; examples thereof include monoethanolamine salts and diethanolamine salts and other amine salts. These salts may be used alone or in combination of two or more.
本発明の乳がんの予防又は治療剤は、ＨＥＲ２陽性乳がんだけでなく、抗ＨＥＲ２抗体等のＨＥＲ２標的医薬が有効でないＨＥＲ２陰性乳がんの予防又は治療に有用である。 The prophylactic or therapeutic agent for breast cancer of the present invention is useful not only for the prevention or treatment of HER2-positive breast cancer but also for the prevention or treatment of HER2-negative breast cancer for which a HER2-targeted drug such as an anti-HER2 antibody is ineffective.
本発明の乳がんの予防又は治療剤は、トラスツズマブ等の抗ＨＥＲ２抗体の投与を受けている動物に投与する用途で用いることが好ましい。本発明の乳がんの予防又は治療剤の別の態様は、抗ＨＥＲ２抗体、並びに、２−ヒドロキシ−１，４−ナフトキノン及び／又はその薬学的に許容される塩を含有する乳がんの予防又は治療剤である。抗ＨＥＲ２抗体とＬａｗｓｏｎｅ及び／又はＬａｗｓｏｎｅの薬理学的に許容される塩とを併用して動物に投与することで、どちらか一方のみを動物に投与した場合と比較して、抗ＨＥＲ２抗体と、Ｌａｗｓｏｎｅ及び／又はＬａｗｓｏｎｅの薬理学的に許容される塩の、それぞれの投与量を低減することができる。このため各成分に対する副作用の症状がみられる動物において副作用を低減することができる。 The prophylactic or therapeutic agent for breast cancer of the present invention is preferably used for administration to animals receiving anti-HER2 antibody such as trastuzumab. Another aspect of the breast cancer prophylactic or therapeutic agent of the present invention is a breast cancer prophylactic or therapeutic agent containing an anti-HER2 antibody and 2-hydroxy-1,4-naphthoquinone and / or a pharmaceutically acceptable salt thereof. Is. By administering the anti-HER2 antibody in combination with Lawsone and / or the pharmacologically acceptable salt of Lawsone to the animal, the anti-HER2 antibody and / or the pharmacologically acceptable salt of Lawsone can be administered to the animal as compared with the case where only one of them is administered to the animal. The respective doses of Lawsone and / or the pharmacologically acceptable salt of Lawsone can be reduced. Therefore, side effects can be reduced in animals that have side effects on each component.
本発明の乳がんの予防又は治療剤は、有効成分として、Ｌａｗｓｏｎｅ及び／又はＬａｗｓｏｎｅの薬理学的に許容される塩、或いは、抗ＨＥＲ２抗体並びにＬａｗｓｏｎｅ及び／又はＬａｗｓｏｎｅの薬理学的に許容される塩の組み合せ以外に、他の薬理活性化合物を含んでいてもよい。 The prophylactic or therapeutic agent for breast cancer of the present invention contains, as an active ingredient, a pharmacologically acceptable salt of Lawsone and / or Lawsone, or an anti-HER2 antibody and a pharmacologically acceptable salt of Lawsone and / or Lawsone. In addition to the combination of, other pharmacologically active compounds may be contained.
本発明の乳がんの予防又は治療剤は，前記有効成分以外に、所望の投与形態及び製剤形態に調製するために、必要に応じて、薬学的に許容される担体や添加剤を含んでいてもよい。このような担体や添加剤としては、希釈剤、賦形剤、結合剤、崩壊剤、滑沢剤、懸濁化剤、溶解補助剤、安定化剤、甘味剤、着色剤、矯味剤、矯臭剤、界面活性剤、保湿剤、保存剤、ｐＨ調整剤、緩衝剤、粘稠化剤等が挙げられる。 In addition to the active ingredient, the prophylactic or therapeutic agent for breast cancer of the present invention may contain a pharmaceutically acceptable carrier or additive, if necessary, in order to prepare a desired dosage form and formulation form. Good. Such carriers and additives include diluents, excipients, binders, disintegrants, lubricants, suspending agents, solubilizers, stabilizers, sweeteners, colorants, flavoring agents, and odorants. Examples thereof include agents, surfactants, moisturizers, preservatives, pH adjusters, buffers, thickeners and the like.
本発明の乳がんの予防又は治療剤の剤型は特に限定されず、投与形態等に応じて適宜設定すればよい。本発明の乳がんの予防又は治療剤の剤型として、具体的には、注射剤、シロップ剤、リポソーム製剤等の液状製剤；錠剤、硬カプセル剤、軟カプセル剤、顆粒剤、散剤、丸剤等の固形状製剤等が挙げられる。また、注射剤にする場合には、使用前に生理食塩水等で溶解する用時調製用粉末（例えば凍結乾燥粉末）の形態であってもよい。
本発明の乳がんの予防又は治療剤は、生体内で乳がん細胞の増殖を抑制することによって、乳がんを予防又は治療する効果が奏される。
The dosage form of the prophylactic or therapeutic agent for breast cancer of the present invention is not particularly limited, and may be appropriately set according to the administration form and the like. Specific examples of the dosage form of the preventive or therapeutic agent for breast cancer of the present invention include liquid preparations such as injections, syrups, and liposome preparations; tablets, hard capsules, soft capsules, granules, powders, pills, etc. Examples include solid preparations of. Further, when it is used as an injection, it may be in the form of a powder for preparation before use (for example, lyophilized powder) which is dissolved in physiological saline or the like before use.
The prophylactic or therapeutic agent for breast cancer of the present invention has an effect of preventing or treating breast cancer by suppressing the growth of breast cancer cells in vivo.
本発明の乳がんの予防又は治療剤の投与対象となる動物は、典型的にはヒトであるが、これには限らず、ラット、ハムスター、モルモット、マウス、ウシ、ヒツジ、ブタ、ヤギ、サル、ウサギ等の非ヒト哺乳動物等であってもよい。 The animals to which the prophylactic or therapeutic agent for breast cancer of the present invention is administered are typically humans, but are not limited to rats, hamsters, guinea pigs, mice, cows, sheep, pigs, goats, monkeys, etc. It may be a non-human mammal such as a rabbit.
本発明の乳がんの予防又は治療剤の投与形態としては、例えば、局所投与、皮下投与、腹腔内投与、筋肉内投与、静脈内投与、経直腸的投与、皮内投与等の非経口投与；経口投与等が挙げられ、適用する動物に応じて適宜設定すればよい。本発明の乳がんの予防又は治療剤の投与形態としては経口投与が特に好ましい。 Examples of the administration form of the preventive or therapeutic agent for breast cancer of the present invention include parenteral administration such as local administration, subcutaneous administration, intraperitoneal administration, intramuscular administration, intravenous administration, transrectal administration, and intradermal administration; oral administration. Administration and the like may be mentioned, and may be appropriately set according to the animal to which it is applied. Oral administration is particularly preferable as the administration form of the prophylactic or therapeutic agent for breast cancer of the present invention.
本発明の乳がんの予防又は治療剤の投与量については、乳がんの種類、投与対象動物の年齢、性別、体重、症状の程度、投与形態等に応じて適宜設定すればよく特に限定されないが、例えば、有効成分であるＬａｗｓｏｎｅ及び／又はＬａｗｓｏｎｅの薬理学的に許容される塩の総量が、１日あたり５００〜５０００μｇ程度となる量を１回又は数回に分けて要とすればよい。 The dose of the prophylactic or therapeutic agent for breast cancer of the present invention may be appropriately set according to the type of breast cancer, the age, sex, weight, degree of symptoms, administration form, etc. of the target animal, and is not particularly limited. , The total amount of the pharmacologically acceptable salts of Lawsone and / or Lawsone, which are the active ingredients, may be about 500 to 5000 μg per day, which may be required in one or several divided doses.
本発明の、乳がん細胞の増殖用製剤は、生体外又は生体内において、各種の乳がん細胞の増殖を抑制する用途で用いることができる。増殖が抑制される乳がん細胞の起源は特に限定されず、上記のヒト又は非ヒト哺乳動物に由来する乳がん細胞であってよい。乳がん細胞はＨＥＲ２陽性乳がん細胞であってもよいし、ＨＥＲ２陰性乳がん細胞であってもよい。 The preparation for breast cancer cell proliferation of the present invention can be used for the purpose of suppressing the proliferation of various breast cancer cells in vitro or in vivo. The origin of the breast cancer cell whose growth is suppressed is not particularly limited, and may be a breast cancer cell derived from the above-mentioned human or non-human mammal. The breast cancer cell may be a HER2-positive breast cancer cell or a HER2-negative breast cancer cell.
１．材料
１．１．活性成分
活性成分の候補物質として、Ｌａｗｓｏｎｅ（２−ヒドロキシ−１，４−ナフトキノン）（東京化成工業）及びトラスツズマブ（Ｔｒａｓｔｕｚｕｍａｂ）（Ｓｅｌｌｅｃｋ Ｃｈｅｍｉｃａｌｓ）を用いた。
1. 1. Material 1.1. Active Ingredients Lawsone (2-Hydroxy-1,4-naphthoquinone) (Tokyo Chemical Industry) and Trastuzumab (Selleck Chemicals) were used as candidate substances for the active ingredient.
１．２．細胞
ＨＥＲ２（ヒト上皮増殖因子受容体２）陽性／ＥＲ（エストロゲン受容体）陽性／ＰＲ（プロゲステロン受容体）陽性のヒト乳がん細胞株としてＢＴ４７４細胞（アメリカン・タイプ・. カルチャー・コレクション）を用いた。
ＨＥＲ２陽性／ＥＲ陰性／ＰＲ陰性のヒト乳がん細胞株としてＡＵ５６５細胞（アメリカン・タイプ・. カルチャー・コレクション）を用いた。
ＨＥＲ２陰性／ＥＲ陰性／ＰＲ陰性のヒト乳がん細胞株としてＢＴ５４９細胞（アメリカン・タイプ・. カルチャー・コレクション）及びＭＤ２３１細胞（アメリカン・タイプ・. カルチャー・コレクション）を用いた。
1.2. Cells BT474 cells (American type culture collection) were used as HER2 (human epidermal growth factor receptor 2) positive / ER (estrogen receptor) positive / PR (progesterone receptor) positive human breast cancer cell lines.
AU565 cells (American Type Culture Collection) were used as HER2-positive / ER-negative / PR-negative human breast cancer cell lines.
BT549 cells (American type culture collection) and MD231 cells (American type culture collection) were used as HER2-negative / ER-negative / PR-negative human breast cancer cell lines.
１．３．培地
ＢＴ４７４細胞、ＡＵ５６５細胞、ＢＴ５４９細胞及びＭＤ２３１細胞は１０％牛血清アルブミン含有ＲＰＭＩ１６４０培地（ペニシリン・ストレプトマイシン含有）で培養された。
1.3. Medium BT474 cells, AU565 cells, BT549 cells and MD231 cells were cultured in RPMI1640 medium containing 10% bovine serum albumin (containing penicillin and streptomycin).
２．実験
２．１．実験１
９６ウェルプレートに１．０×１０４細胞／ウェルで前記培地中のＢＴ４７４細胞及びＡＵ５６５細胞を播種して、１日後に終濃度０μＭ、１μＭ、３μＭ又は１０μＭのＬａｗｓｏｎｅ及び終濃度０．００５ｎｇ／ｍＬ、０．０５ｎｇ／ｍＬ、０．５ｎｇ／ｍＬ又は５ｎｇ／ｍＬのトラスツズマブを添加し、３日後にＣＣＫ８アッセイを行い、相対細胞数を求めた。
2. 2. Experiment 2.1. Experiment 1
BT474 cells and AU565 cells in the medium were seeded in a 96-well plate at 1.0 × 10 4 cells / well, and one day later, a final concentration of 0 μM, 1 μM, 3 μM or 10 μM Lawsone and a final concentration of 0.005 ng / mL. , 0.05 ng / mL, 0.5 ng / mL or 5 ng / mL of trusszumab was added, and 3 days later, the CCK8 assay was performed to determine the relative cell number.
ＣＣＫ８アッセイとは、Ｃｅｌｌ Ｃｏｕｎｔｉｎｇ Ｋｉｔ ８（ＣＣＫ８、株式会社同仁化学研究所 ＣＫ０４）を用い、細胞数を相対値として求めるアッセイである。ＣＣＫ８アッセイは、すべての細胞においてＲＰＭＩ１６４０培地（フェノールレッド非含有）で実施された（以下同じ）。 The CCK8 assay is an assay in which the number of cells is determined as a relative value using Cell Counting Kit 8 (CCK8, Dojin Chemical Laboratory Co., Ltd. CK04). The CCK8 assay was performed in RPMI 1640 medium (without phenol red) in all cells (same below).
結果を図１に示す。Ｌａｗｓｏｎｅは、トラスツズマブの存在下において濃度依存的にＨＥＲ２陽性細胞であるＢＴ４７４細胞及びＡＵ５６５細胞の増殖を抑制したことが確認された。 The results are shown in FIG. It was confirmed that Lawsone suppressed the proliferation of HER2-positive cells BT474 cells and AU565 cells in a concentration-dependent manner in the presence of trastuzumab.
２．２．実験２
９６ウェルプレートに１．０×１０４細胞／ウェルで前記培地中のＢＴ４７４細胞及びＡＵ５６５細胞を播種して、１日後に終濃度０μＭ、１μＭ、３μＭ又は１０μＭのＬａｗｓｏｎｅを添加し、３日後にＣＣＫ８アッセイを行った。ｎ数は４とした。
2.2. Experiment 2
BT474 cells and AU565 cells in the medium were seeded in a 96-well plate at 1.0 × 10 4 cells / well, and 1 day later, a final concentration of 0 μM, 1 μM, 3 μM or 10 μM Lawsone was added, and 3 days later, CCK8. The assay was performed. The n number was 4.
結果を図２に示す。図２中、有意な減少は、相対細胞数０．７５以下かつＬａｗｓｏｎｅを含まない（終濃度０μＭ）の相対細胞数に対してｏｎｅ−ｗａｙ ＡＮＯＶＡ Ｄｕｎｎｅｔｔ抽出でＰ＜０．０１のとき＊＊で示し、Ｐ＜０．００１のとき＊＊＊で示した。 The results are shown in FIG. In FIG. 2, the significant decrease was ** when the number of relative cells was 0.75 or less and the number of relative cells did not contain Lawsone (final concentration 0 μM) and P <0.01 by one-way ANOVA Dunnett extraction. It is shown and indicated by *** when P <0.001.
この結果から、Ｌａｗｓｏｎｅは、単独で、濃度依存的にＨＥＲ２陽性ヒト乳がん細胞であるＢＴ４７４細胞及びＡＵ５６５細胞の増殖を抑制したことが確認された。 From this result, it was confirmed that Lawsone alone suppressed the proliferation of BT474 cells and AU565 cells, which are HER2-positive human breast cancer cells, in a concentration-dependent manner.
２．３．実験３
９６ウェルプレートに１．０×１０４細胞／ウェルで前記培地中のＢＴ５４９細胞及び５．０×１０３細胞／ウェルで前記培地中のＭＤ２３１細胞を播種して、１日後に終濃度０μＭ、１μＭ、３μＭ又は１０μＭのＬａｗｓｏｎｅを添加し、２日後にＣＣＫ８アッセイを行った。ｎ数は４とした。
2.3. Experiment 3
BT549 cells in the medium at 1.0 × 10 4 cells / well and MD231 cells in the medium at 5.0 × 10 3 cells / well were seeded on a 96-well plate, and one day later, the final concentration was 0 μM and 1 μM. 3, μM or 10 μM Lawsone was added and a CCK8 assay was performed 2 days later. The n number was 4.
結果を図３に示す。図３中、有意な減少は、相対細胞数０．７５以下かつＬａｗｓｏｎｅを含まない（終濃度０μＭ）の相対細胞数に対してｏｎｅ−ｗａｙ ＡＮＯＶＡ Ｄｕｎｎｅｔｔ抽出でＰ＜０．０１のとき＊＊で示し、Ｐ＜０．００１のとき＊＊＊で示した。 The results are shown in FIG. In FIG. 3, the significant decrease was ** when the number of relative cells was 0.75 or less and the number of relative cells did not contain Lawsone (final concentration 0 μM) and P <0.01 by one-way ANOVA Dunnett extraction. It is shown and indicated by *** when P <0.001.
Ｌａｗｓｏｎｅは、濃度依存的にＨＥＲ２陰性ヒト乳がん細胞であるＢＴ５４９細胞及びＭＤ２３１細胞の増殖を抑制したことが確認された。
It was confirmed that Lawsone suppressed the proliferation of BT549 cells and MD231 cells, which are HER2-negative human breast cancer cells, in a concentration-dependent manner.
Claims (4)
A growth inhibitor for breast cancer cells containing 2-hydroxy-1,4-naphthoquinone and / or a pharmaceutically acceptable salt thereof as an active ingredient.
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